Loading summary
Transcript207 lines
- [00:02]
A
Welcome to season three of Derms on Drugs, a video podcast brought to you by Scholars of Medicine. The best educational platform in dermatology and provided a no cost to medical providers. Terms on drugs is where cutting edge derm meets hit or miss comedy. I'm Dr. Matt Zyers from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 70 years of combined derm experience to discuss, debate and dissect the hot est dermatology. It is everything you need to know to be on a cutting edge of derm and you'll actually have some fun listening. New episodes drop every Friday on Scholars of Medicine, Apple Podcast, Spotify and other major podcast platforms. And I highly recommend that you download the Scholars of Medicine app to access the full podcast video archive. Explore the best educational content in all of derm real pharma independent coverage of all of dermatology supported by an amazing AI clinical consultant called Ask Simon. So this week we've got another one of our patented six pack episodes and we actually have Dr. Patton coming to us live from Italy. And it turns out that when he's in Italy, he actually has better Internet than he does whenever he's at home. It's kind of shocking. Maybe that means he needs a tech upgrade, but we'll see. But Dr. Patton, how was the trip to Italy? You just got there last night.
- [01:24]
B
No, I been here. Well, I can't remember. I got here on Sunday. What's today? Monday. Yeah, we'll call that yesterday morning. Sunday morning.
- [01:36]
A
It's yesterday to the rest of us.
- [01:38]
B
Yeah, yeah, I left on Left America on Saturday and got here Sunday morning.
- [01:44]
A
Where are you right now?
- [01:46]
B
Florence.
- [01:47]
A
Oh, have you been to Florence before?
- [01:50]
B
I have, yeah.
- [01:51]
A
Okay, because the Ferris. Have you been to Florence?
- [01:54]
C
I have not. I'm not as in the least sophisticated, apparently.
- [01:57]
A
That's true. She's not been for our listeners. She has been to neither Venice nor Florence. So it's probably never even seen the Leaning Tower of Pisa. You know, that's the, the, I, I will say for any of our listeners who've not been to Florence, being in the same room as the statue of David, like, I, it feels like it's radiating some like this energy. It was really crazy. I like stood there for two hours and just was like, man, it was, it was nuts. I don't know. Patton, did you experience anything like that when you went to see the statue of David?
- [02:33]
B
I haven't gone yet. It's on the schedule, but it hasn't. Haven't gone yet.
- [02:37]
A
Okay.
- [02:37]
C
All right. For the nuts.
- [02:39]
B
I felt that way with the Sistine Chapel. That.
- [02:43]
A
Okay.
- [02:43]
B
That kind of like. I just got this vibe of like, man.
- [02:47]
C
Yeah, I would agree. And I have been to Rome. Those of you.
- [02:51]
B
Oh, you don't have to, you don't have to make stuff up.
- [02:53]
A
Yeah. She's been, well, she's been to the common parts of Italy.
- [02:56]
B
She's been to Rome, Texas.
- [02:58]
A
She probably had a. Probably a layover on her on her way to somewhere in Eastern Europe.
- [03:05]
C
Shoulders covered, knees covered, did it all.
- [03:09]
A
Okay. All right. Yeah.
- [03:10]
B
Yeah.
- [03:10]
A
All right, let's. Let's get into it here. Ferris, what do you got to lead us off?
- [03:14]
C
Okay, so today is melanoma Monday for me, even though it is June already, but this is melanoma Monday. So I am going to start with a paper that was in the bjd, and this is entitled Impact of Clinical Pathologic Features on the Prognosis of Thin Melanomas. A Retrospective Cohort Analysis. Beagles at all. Semenov was the corresponding author. So what is this about? This is like, you know, we think, ah, thin melanoma, no big deal. Right. But, you know, sometimes that's not the case. There are those thin melanomas that are recurrent or metastatic. And so they looked at comparing not, you know, non recurrent versus recurrent melanomas or low versus high risk thin melanoma. So all of these are melanomas a millimeter or thinner. Generally, they're stage one. They've been, you know, excised. And so these are the ones that you're like, okay, good. But interestingly, when you look at data, they thin melanomas count for about 30% of melanoma deaths. That's more because there's just lots of them, not because most 30% of them will kill you. But, you know, it's hard sometimes to know, you know, knowing that we can have, you know, metastatic melanomas that are T1A or that stage 1A or stage 1B. You know, how can we get an. An inkling into which ones might be the bad actors without just treating them all as bad? Okay, so design retrospective cohort story from Mass General, Brigham and the Dana Farber Patients diagnosed between 2000 and 2015, stage 1A or B melanoma with a tumor thickness of a millimeter or less. And that was biopsy plus six decision. They looked at demographics, comorbidities, tumor features, recurrent status and type and cause of death from EHR cancer registry. And so they were only considered non recurrent. They only put, you know, patients in the non recurrent bucket if they had at least five years of follow up. So, you know, recurrence, it could be shorter. Non recurrence was five years. And so, so what did this look like? This cohort size 802 patients within melanoma, 71 had recurrences. That's about 9%. And how did they look? They were a bit older, like you might expect 61 versus age 57 for the non recurrence. And sex distribution was pretty similar. So what was predictive of recurrence in, you know, what were already thin melanomas? High mitotic rate. That was, you know, a big one. Odds ratio 1.28 per additional mitosis per millimeter squared. So that was one. The other one that's interesting was presence of tumor infiltrating lymphocytes. So my first thought was, yeah, yeah, you got tills. That's a better prognosis. Not the case actually. Having TILLS was associated with a worse prognosis odds ratio of 3.26 and then another one that we, you know, might expect, which is the absence of a radial growth phase. So odds ratio of 7.52 if they saw no radial growth phase for 5 year melanoma specific survival, being not uninsured or self paid, which is basically uninsured, was associated with kind of dramatically worse outcomes. Hazard ratio of 29.55 year overall survival was linked to, you know, higher Charleston comorbidity index, which is basically like, you know, taking into account all your other comorbidities.
- [07:03]
A
You're, you're like Patton. Okay, you know, probably have an aortic valve that's about to blow at any second.
- [07:10]
C
Exactly. Bad heart, you know, poorly traveled, stuff like that. Mitotic rate. Higher mitotic rate also associated with worse overall circulation survival as well as that absence of the radio growth phase. So you might think, okay, thin, less than a millimeter, you know, is that, does that matter? So it didn't. So if they just said, well let's consider 0.8, you know, less than versus 0.8 or higher as the cutoff, no difference. If they could treat it as a continuous variable, you know, where didn't matter. So within that 1 millimeter thickness, it wasn't like there's thickness thin, thin T1s and thick T1s. It was just, no, it was really just the factors that we talked about. So radial growth Phase tills be no radial growth phase bad prognosis, tilt tills present bad prognosis and then higher mitotic rate associated worth a worse prognosis. So what, what do we take away from this? So mitotic rate like it makes sense. So if you start to see, you know, one mitosis, I don't worry. But when it's like five or six, I, I start to be a little bit concerned. The, the till thing was interesting. The authors speculate that, you know, maybe these were sort of these exhausted non cytotoxic like regulatory T cells being present. They don't really have any data for that. That was speculation. And then the absence of the radial growth phase is kind of interesting. Like I guess the way that I think about it is, you know, when we, I think a lot about you know, melanoma screening and you know, we always like, we kind of consider like lots of thin melanomas as over diagnosis. But you know, in a way, you know, what we're really trying to do with screening is to basically find those lesions, I think that maybe have a vertical growth phase and where we think we're going to like intervene just in time, just before they get too deep and go back and excise those. So you know, it would suggest that you can be. All thin melanomas are not created equally. This would say about 9% of them, if they really did this in a systematic sequential way and didn't sort of pick out cases, have some potential to, you know, have a bad outcome. So I guess when we're screening we're really trying to find those 9% and intervene as quickly as possible before they metastasize. Maybe that's a way to think about it.
- [09:46]
A
Ferris, what is your. So first, the immediate question that jumps to mind. For me, this is exactly the group that people would normally be like, oh, these are the people that we should use Castle for, you know, thin melanomas and blah blah, blah. As you guys and I have changed from being a we should use Castle and everybody to a we should never use Castle. It's a terrible test. Eventually we'll do an episode just about Castle and why I now think that. But so is would does so we argue about this Castle change anything? Does any of this change anything? For what is this going to play into any decisions you make?
- [10:29]
C
You know, I think that when you are having the. Do we, you know, more frequent follow up maybe, um, do we want to, you know, consider sentinel nodes so you know, when patients are on that border of being right around 0.8 if they had more of these risk factors. I don't know what to make of the till. I'm going to put that on the back burner in terms of what I'm going to think. But you know, I would say higher mitotic rate. That's going to push me toward, you know, saying sentinel nodes so that we have the ability to follow them a little bit more carefully. Absence of radial growth phase. That gets me a little bit more nervous. You know, maybe this will be somebody who I follow more carefully. I mean, we don't have prospective data to say, ah, what we need to do now is image you or send you when you're thinner or you know, anything else like that. Like it doesn't give me actionable data. But you know, I guess what you could also say is we don't, you know, maybe what we should be doing is like prospectively following do the prospective trial, you know, like you don't necess gene expression profiling is just one thing to put into a model of deciding how high risk a patient is. You know, maybe we should look at what if we did this just with mitotic rate, till and you know, absence of radial growth factor. You know, I, I don't know. I can't remember if they actually had like sentinel node positivity and things like that in here. I don't think that they looked at that at that degree. So.
- [12:03]
A
Okay, interesting. Pat, do you have any takeaways on this?
- [12:07]
B
This is such a small target of patience though, isn't it? Like anything.
- [12:13]
C
I mean, it's 800. That's not nothing.
- [12:17]
B
No, I know, but what I'm saying is if you come up with a plan to say, okay, you have more tills and so I'm going to change my how we follow you up. The most of the people that you follow up with like more tills are probably going to be okay. So aren't you like just increasing everything to pick up like, I, I can't see anything make like being cost effective or not without risk of overworking people who eventually don't go on to become anything. You know what I mean? Like we're, we're, we're kind of getting to the point where like just keep doing what we do for these patients. It's unfortunate that this happens, but how are we going to change anything? Clinically that's going to make a big difference and not going to increase working up and following patients that actually are going to be okay. Right?
- [13:08]
C
Yeah. I mean, I think that again, it kind of goes into the decision making. And again, these are all in the patients. These are all the patients for whom would fall under NCCN guidelines into discuss and consider. Sentinel node biopsy. None of these are like 100% recommend. So these are all in that discuss and consider. So I think that being able to say, you know, you got to have things you consider, it's not just, I don't know, right. You say, why would we consider?
- [13:39]
A
It's pitch fairs. I've never. That's never occurred to me. People you should consider. Well, you've got to have stuff you should consider that's. That's actually really useful.
- [13:51]
C
Yeah, I mean, consider isn't just like pontificate. It's. Here's why. Here's what you would take into consideration. Here are some high risk features or you don't have these, or what? I mean, there's a lot of things. What would you do if it were positive? What would you do if you're negative? You're gonna do the same thing then.
- [14:06]
A
Yeah.
- [14:07]
C
Maybe don't do a procedure.
- [14:08]
A
Okay, well, that's us. Every once in a while, fair. Most of what you say, I'm just. Every once in a while you get a good. You get a good once in a while.
- [14:17]
B
Okay.
- [14:18]
A
All right, Patton, what do you got?
- [14:20]
B
All right, my first six pack paper from February 2026, JAD and is titled Biologic Therapy plus Oral Oxybutynin Chloride and hydradinitis Supper tiva, a potentially valid therapy to moderate acute flares by Molinali et al. There's a study performed at the Polytechnic Marca University right here in Italy, which is where I am.
- [14:44]
C
Are you going to Italian papers?
- [14:46]
B
Are you? I, you know, I was going to do this other Italian one and I. I couldn't access the journal. I traveled all the way to Italy. That was such a waste of money. I still couldn't access.
- [14:56]
A
Your whole trip is now tax deductible. Patent. Yeah, yeah, you got to stop over
- [15:01]
B
there, get my tax lawyer on that. All right. Yeah. So this group had an earlier paper evaluating oxybutynin as monotherapy. Nhs. This paper is a similar study.
- [15:12]
A
Wait, was it the monothec? Because there was one where they did, like, antibiotics. Somebody did antibiotics and then they did oxybuty at the end of the antibiotics, and it extended how long before people flared? I. Is that a difference? Not the study you're talking about.
- [15:28]
B
I don't know. I didn't open that study. I. I pulled it up on Pubmed and it was like in 2023. J EAD.
- [15:35]
A
That was it.
- [15:35]
B
And that was the title of the article. I didn't go into it.
- [15:38]
A
Yeah, yeah.
- [15:39]
C
And he's like, I'm only reading Italian papers.
- [15:41]
A
Only Italian this week.
- [15:42]
C
Yeah.
- [15:43]
B
Yep, yep, yep. All right, so this was prospective study. 25 patients in each group. Group A started adalimumab plus oxybutyn, and group B started adalimumab alone. They didn't get into the dosing. I'm sure it was the standard HS dosing. Adalimumab, I.e. oxybutynin, was dosed 5 milligrams for the first week, 7 and a half for the second second, and then 10 milligrams for the duration of the study. Both groups were followed for 48 weeks. Evaluations were done at baseline, 24 weeks, and 48 weeks by blinded evaluators. So it wasn't like a randomized double blind, blah, blah, blah. But the evaluators, they didn't know what the patients were treated with. So that's pretty good. Table two kind of lays it out there. The improvements in the oxybutynin adalimumab group were statistically significantly better than the adalimumab alone. And multiple measured outcomes. My video went funny there. So mean IH4 scores, pain, pruritus scores, nodules, abscesses, DLQI number and duration of flares. Small numbers difference, but it was all statistically significant, favoring adding oxybutynin to adalimumab. So it seemed like oxybuty helped. So maybe we start adding this on. What did you guys think?
- [17:07]
C
It almost was like, I saw that paper briefly. What was their. Like, mechanistic thought.
- [17:14]
B
You decrease sweating even in patients who didn't have. So, you know, the number of people that had hyperhidrosis versus non hyperhidrosis was like the same. Uh, so whether the patients had hyperhidrosis, not hyperhidrosis, the oxybutynin still worked. But they still say that you sweat less. Sweat does contribute to the microbiome.
- [17:36]
C
We.
- [17:37]
B
We think microbiome, like bacteria, has something to do given the effectiveness of ertapenem. And so their theory is you're altering the microbiome by. By changing the sweat, the amount of sweat on the skin, and that contributes to improvement.
- [17:52]
C
And people have done Botox, like. Like, you know, regional Botox for hs, and there's kind of some efficacy with it. So, I mean, then why not do. What's that?
- [18:06]
B
Yeah, I mean, with, like, the HS we had the. The UNC guy on. I'm blanking. It's late. And I'm in Italy. Chris Sed and then we talked to Dave Lou like when they, when they have given their HS talks I don't think they talk about sweating at all. I don't think they talk about botox. I don't think they talk about oxybuty. So is this real? I don't know.
- [18:31]
A
I, I, I th percent buy it. Th percent buy it. We know it's it is, it's a
- [18:38]
C
low, it's a small study, very poorly controlled mat is all it is all over it.
- [18:44]
A
I am all over it.
- [18:47]
B
Do you worry about oxybuty and dementia?
- [18:50]
A
Oh yes, that's so my, my question was going to be like should we be doing glycopyr oxybuty in these people? Because glycopyrlate there is no dementia risk because then crush your blood brain barrier. But you might have to take it two or three times a day but it makes it and by the way I'm calling it right now I am claiming the the title in dermatology of the king of low quality evidence. That is my.
- [19:20]
C
That's what you want.
- [19:21]
A
That's what I want to be the, I want to be the leader in low quality evidence.
- [19:25]
C
That's what you are.
- [19:26]
A
Yes, yes. But so I think it makes sense. I mean we know that it's got to be related to not just apocrine glands but sweating in general because people get it in their areas that are non classic apocrine areas. And so I think it's more of an occlusion disease and I think that this makes sense to me. I'm going to start adding some glycopyrrolate onto people.
- [19:52]
C
Okay, here's my proposed clinical trial. If you want to design a small, not very well designed underpowered study because
- [19:59]
A
I know you would love to low quality.
- [20:03]
C
How about Q Braxa wipes, glycopyrrolate wipes kind of do like what insight did with topical rucks and you do like take early stage disease. You wipe down once or twice with Q Braxa wipes and see if you can prevent, you know, if you can treat earlier stage disease.
- [20:25]
A
Here here's even so that's I actually want to be the king of no evidence, just low quality. Even better no evidence. We should start compounding oxybutynin or glycopyrrolate together with a topical jack. It'd be like all that's I think we just cured hs.
- [20:46]
C
All right, done. We're gonna just quit talking about it. We've figured it out.
- [20:50]
A
We're done.
- [20:50]
C
You can get compounded glycopyrrolate spray.
- [20:54]
A
Yes, I know. Just throw some JAK inhibitor in there.
- [20:56]
B
You could.
- [20:57]
A
It's all done.
- [20:58]
C
And compounded tofacitinib. So you could do your glycopyrrolate then add some tofacitinib.
- [21:04]
A
Right, Done.
- [21:06]
C
Karma, middleman. Get it all compounded. All right.
- [21:09]
A
Just for all. For all of our patients. Can. For all of our listeners. Can you imagine what kind of amazing treatment got. Patients got when the three of us were residents at the University of Pittsburgh, standing out in the hall. I don't know what to do for them. Do you know what to do?
- [21:23]
C
And you guys were the ones who taught me.
- [21:28]
B
So scary.
- [21:29]
C
So scary. We killed nobody, though.
- [21:32]
B
That's what led to, like, photodynamic therapy for a patient with Darius.
- [21:36]
A
Oh, I'll never forget. I remember that there was an article about it. It was an article. So it was.
- [21:42]
C
It was like a case in a impact factor 0.2.
- [21:46]
B
A low quality article. And Matt was like, yep, I'm signing you up.
- [21:50]
A
So we. It's so by the. This was for anybody who's listening before. This is the woman that Patton and I almost killed with the full body electron beam therapy for Darius. I was desperate for, like, anything to do with this woman. So I photoshop her. Her neck and then put her in the, you know, the thing. Turned the light on, went to see another patient. I'm in the other room here, the patient, and I hear back here, and I'm like, what's. I go out in the heart.
- [22:20]
C
Help.
- [22:22]
A
Oh, my God, help.
- [22:24]
C
Because it was so painful. Bad. Yeah, that was. Maybe that's not a good treatment.
- [22:30]
A
No, no.
- [22:31]
C
I know your heart was in the right place.
- [22:33]
A
Yes. I was trying to try to do
- [22:35]
C
anything that could work. I have also. I also saw that patient for a while, so it is tough, but yes. Yes.
- [22:41]
A
All right, all right. Let's. Let's. You guys got anything else or go on to mine?
- [22:45]
C
Go on to yours.
- [22:46]
A
All right, so I'm going to do my more real one first. So this was an article out of China, and it was about dupilumab facial erythema. And this was to some extent just another confirmation of what we already know, because I still hear people lecture and talk about this who just don't know what they're talking about. So do Pilumab associated facial erythema. This was. So this title was Characteristics and Risk Factors of Dupilumab Associated Head and Neck Dermatitis in Patients with Atopic Dermatitis, the basic takeaway. So looked at a whole bunch of patients who ended up 130 patients who received dupilumab, and some of them got head and neck, the dupilumab facial erythema. Some of them did not. And what they found was that the two predictors were being over the age of 12 and having atopy. So comorbid allergic rhinitis or an IGE that was above 1500. So those, those were the only two things they found that correlated with it. And it confirms again for us what this, what the facial erythema is. So we know head and neck atopic derm. And just for any of our listeners, head neck atopic derm is whenever you have somebody whose atopic derm is worst on their face, neck, upper chest, think areas that they get seborrheic dermatitis. Those patients are allergic to malassezia. It's probably more ige. It might be a little bit T cell, but those people are allergic to malassezia in addition to regular atopic derm, and they do not do well on anything. So these are the patients who often will fail multiple biologics, fail a jack, they fail everything. You put them on a little itraconazole and they get better. You do itroconazole, 200 milligrams a day till they're better. Then once they're better, you do the itraconazole Saturday and Sunday only. Dupilumab facial erythema is a variant of this. And so it's people who are. And we have data on this from some other studies that showed elevated, specifically antimalassia IGE is associated with. It's the, the most predictive thing of papillomy facial erythema. And so, see, people have an underlying sensitivity to malassesia. When you put them on doopy, we get the immune shift towards TH17. TH17 is, is how your body reacts to Malassezia. It's driving SEP Derm. And so you get this overlap ad subderm picture. This is facial erythema. Every one of those patients who has dupilib facial erythema, you should assume that's what it is. You should put them on triconazole.
- [25:25]
C
And.
- [25:25]
A
And then if they don't get better, then you think, okay, maybe this is demodex, maybe this is contact derm. Maybe this is something else. They're not all malassezia, but probably 80, 90% of them are.
- [25:40]
C
Okay, Matt, Itraconazole, not like fluconazole.
- [25:43]
A
So you can do fluconazole. But we have some literature on it and itraconazole is. Is substantially better now by Mad Zyre's evidence standards. So there were like seven patients that somebody. They didn't get better on fluconazole and they switched them to itraconazole. So that is conclusive evidence. But mechanistically. Mechanistically. Right. So fluconazole is water soluble. That's why it's a good drug for mouth and vagina. Itraconazole is lipid soluble. So it is a much better drug for the seb derm spectrum of stuff. So itra, the small amount of literature we have says ITRA is better. And itra's gotten cheap. Right. So it's not like it used to be where it was.
- [26:24]
C
Yeah, it's interestingly hard to find sometimes, huh. I have just had this. I have a horrible tinea case and like I. Which I think is multi drug resistant. I cannot. It. It was like calling all over to pharmacies to be like, I guess I've got 30 pills, I've got. The pharmacist called me back and said how about voraconazole? I was like, you know what, we're not going to jump right to voriconazole. Maybe we'll just.
- [26:49]
B
Amphotericin D. Yeah, amphoteric.
- [26:52]
C
Garrison. Yeah, yeah, Call around and order Itraconazole.
- [26:56]
B
So yeah, I have a question. So the ige malassezia. Now one of the things like doopie's supposed to actually like work against class switching.
- [27:06]
A
Yes. So what I think is happening. What I think is happening. The. I think the ige is a marker that people probably also have T cells because we don't. There is some work looking at T cell reactivity to malassesia and that has been shown in these patients as well. But there's a lot of commercial labs can do malassezia ige. So we have a lot more data on it. I think it's just a marker of. In general, like you are allergic to
- [27:34]
B
the ige could actually.
- [27:36]
A
Yes.
- [27:37]
B
Get better.
- [27:37]
A
But your immune system is reactive to this to malicesia.
- [27:43]
B
Okay.
- [27:44]
A
Yeah. All right, all right. That's it. So but. Oh yeah. So the take away the things. So right. There was over the age of 12 because head and neck dermatitis always has its onset after puberty. So it's like once they would start to get acne that tells you now they have more sebum. So their malassezia, it can have its onset anytime. After puberty. But most commonly it's its onset during puberty and then elevated IGE to tell you that they're at atopic and susceptible to developing allergy to malassezia. All right, that's it. All right, Ferris, what's number two?
- [28:17]
C
Okay, this is like the serious one. Not that the other one wasn't, but prevalence of familial melanoma genes and cancer risk among genomically ascertained individuals. This was recently in jamaderm, Goldstein et al. Okay, so this is kind of looking at this. You know, this comes up, people ask me all the time, when do you do genomic testing or, you know, genetic testing for patients with melanoma? And if, know, I always kind of say like, oh, if they've had three or more invasive melanomas, and especially if the first one was before the age of 50 or there's three in the family or there's like, you know, melanoma, melanoma, pancreatic cancer. So that's kind of the answer I've always given. But they looked at this a little bit differently. So they looked at just, you know, they looked at patients. They didn't say, you have melanoma, we've tested you, here's what we found. They, they looked at, you know, over almost 700,000 people who had had their, you know, genome ascertained either through the UK Biobank or the Geisinger My code. And then they asked sort of the smart question, if you start with the genotype instead of the phenotype, what do you learn about the familial melanoma genes and their cancer risk? And they looked at melanoma risk, but then they also looked at sort of overall cancer.
- [29:40]
A
So wait, wait, let's get for what? So they looked at, they started with genome, found the people with the high risk genes, and then said, how many
- [29:49]
C
melanoma did they get?
- [29:50]
A
Melanoma? Because we've never really been able to look at that before because you just have to have a bunch of random people that you got it in.
- [29:55]
C
Yeah, now that we started doing that, we can actually start to ask these questions. So, okay, so the big eight major familial melanoma genes that they studied were, they were eight, they were BAP1, CDK, N2A, CDK4, MITF E318K, Pot1, Turf2IP Inter Promoter.
- [30:22]
A
And so how did you just give away your password?
- [30:25]
C
I did, yeah. Shoot, that also the name of my next dog. But yeah, the combined pathologic variant program prevalence was 0.5% in the My Code and 0.9% in the UK Biobank. So you know, that was basically at a population level a little under 1%.
- [30:44]
A
So how many people had. That's how many people had at least one of these.
- [30:47]
C
Had at least one of those. Interestingly, the most common one was MITF E318K and then the next most common was. Well, so that was the most common. And then the next most common group were the CDKN2A, Pot 1, BAP1 and then ACD, CDK4, blah blah blah, those were the least common ones. So while like I was like mitf, I don't really think about that. Like I think a CDK N2A. You know, there are many more people who harbor this MITF mutation, but you can think of it as like having lower penetrance in terms of the abscess absolute outcome. Okay, I can. If anybody is super interested, I'm going to give you the high level of what they do because it's good like boards review fodder because I know all my residents listen to me rapidly. Okay. BAP1, it's a D ubiquitous tumor suppressor gene. CDK N2A encodes P16Inc4A and P14ARF which are cell cycle checkpoint proteins. MITF is M is the, is a melanocyte master Transcription factor and E318K is a variant that's a moderate risk allele sort of, you know, lower penetrance. Pot 1 is in the shelterin complex of genes that protects telomeres and ACD and turf 2IP are also sheltering genes that help to maintain contain telomeres. And then the TERT promoter also is involved in telomere regulation. So lots of telomere related genes. Okay. That was where the basic science education ends. Okay. In both cohorts, melanoma risk was increased Primarily for the CD, CTK, CDKN2A, MITF E318K and POT1 gene mutations. And it was MITF and CDKN2A carriers who developed melanoma significantly earlier than non carriers. So they do have a, you know, a Kaplan Meier curves and they show that they start separating in the fourth decade of life. So that is kind of helpful because you're like, all right, if their family has, you know, MITF E3 3, 18K or CDKN 2A, think about starting screening, you know, more like fourth decade of life.
- [33:16]
A
So in their 30s, should you prophylactically just remove all their skin?
- [33:20]
C
Yes, Matt, that's What you should do. I read that in the journal of, you know, something low quality evidence of low quality derm. No, not remove all their skin back one actually did not have a very significant association, but there were fewer than 50 carriers per cohort. So it may have been, even though it's pretty big underpowered to look at that. My bias with BAP1 is I actually think that they carry a diet, they have these BAP one associated, you know, epithelioid, almost like spitzoid looking lesions. I think historically that the BAP1 or BAPomas have been called melanomas. And that's where a lot of that came in. I mean, I think there are still some melanomas in that population, but I think it seems higher because I think there's been misclassification of these spitzoid bapomas. Okay, broader cancer spectrum Important CDKN2A associated with melanoma, pancreas, which we knew. But they also saw brain, head, neck, and in at least one of the cohorts, breast, biliary tract and non melanoma skin cancer. So that was kind of interesting. The ones that held up after, you know, statistical correction were pancreas, brain melanoma, head, neck, biliary tract and non melanoma. So, you know, those were new. You know, think about, you know, those patients who have CDKN2A. They really are pretty high risk for cancer overall. MITF mutation associated with also kidney cancer, which has been talked about in the existing literature. But they also saw some associated with cervix, nasal cavity, middle ear and non melanoma skin cancer. POT one associated with not just melanoma, but thyroid cancer and Hodgkin's lymphoma and non Hodgkin's lymphoma and myeloma. So there is sort of this hematologic malignancy signal with Pot 1 mutations. And then BAP1, they also saw a prostate cancer association. So I thought this was sort of interesting. It's like a way to look at this, you know, differently. The other thing that so takeaways consider the place where they did see like higher rates of mutations are the group who got melanoma before the age of 40. So I've kind of said like before the age of 50. But really consider this in patients who've had multiple primary melanomas and melanomas before the age of 40. And then like more keratinocyte carcinomas kind of went along with that too. And then the other thing was that they use this like benchmark. There's this idea that you know, when should we test for. You know, when should we do genetic tests? Like when our pretest probability is greater than 2.5%. So they. This kind of met the match. So if you use the threshold of multiple primary melanomas melanoma before the age of 40, then you do have sort of a leg to stand on. The pretest probability is 2.5% or greater.
- [36:33]
B
Have you guys ever sent a patient for gene testing for. I've never done this is not on my radar at all. Because you know, if you, you would have to get like a good. With all these different cancers. If a patient had one primary melanoma and a first. First degree relative with cervical cancer, is that like.
- [36:54]
C
No.
- [36:54]
B
Oh my gosh, you could have. It's not enough.
- [36:58]
C
No. They would have to have a primary melanoma before the age of 40 or multiple primary melanomas. And particularly with one before the age of 40.
- [37:08]
B
So then. So have you ever sent anybody for genetic screening?
- [37:12]
C
I've said yes. I send them to the, to the genetic counselors to discuss. Okay, there's a lot.
- [37:17]
B
So you're not ordering the next gen sequencing yourself. You're like, go talk to genetic counselors. Counselors. You had two primary and invasive. Right. We're not talking inside.
- [37:26]
C
Yeah, we're not talking about insight too invasive. Particularly before the age of 40. You know, if you throw in, you know, family history, if there's something that looks like either BAP1 mutation or CDKN2A, I will, you know, dig into that a little bit more. The BAP one thing in this study, like mesothelioma, I think did not show up in this. And like we know that's an association with BAP1 mutation. So I think it's a little underpowered to make dramatic conclusions. But yes, I will. I send them to genetic counselors. They talk to them and have the discussion about whether or not they want the testing. I will tell patients if, if they don't want to do it.
- [38:02]
B
Like say if you've had. If you have an invasive melanoma and a first degree relative with pancreatic. Yes, send them. So sometimes it is only one melanoma if a relative has another and. But they go through and name all these cancers. So where do you draw like pancreatic. Yes, you. You suspicious for CDK N2A.
- [38:24]
C
So where. So it is where there is a high associ. Like this is one study that picked up a signal. I'm not going to Change sending to genetic.
- [38:32]
B
Okay, okay. That's what I was confused about. I was like, so what are they telling us to. Who are they telling us to refer these days?
- [38:40]
C
No, it's really more before the age of 4, 40. And that is more helpful than to me than before the age of 50. Right. That cuts out a group. So I think it is helpful and it's a discussion. And I tell patients like, even if you, you know, somebody's had four primary melanomas and they test negative for one of the genes, I'm like, I'm not gonna. It doesn't really change what I'm gonna do. Right. I know you're at risk. You've had multiple primary melanomas. You're going to keep seeing me. So they need to think about that. But I thought this was really the first time we've taken a huge population, said who identified, who had the jet black. People got tested, but people just had that and then followed them.
- [39:17]
B
Yeah, yeah. I just, I was so confused by the end of it, I'm like, I guess we just refer anybody. But I think I got a little too excited here in Italy.
- [39:27]
A
And you can't just get 23 and me done now. Okay, that was a joke. In case. I love it when I say something that's supposed to be dumb. And Ferris answers me very seriously.
- [39:41]
B
He may actually be seriously asking me this question. I need to take it seriously. Yeah.
- [39:46]
C
Yes, yes.
- [39:48]
A
It's not unreasonable. Not unreasonable. All right, let's go, Patton, what do you got?
- [39:53]
B
All right, October 2020, I. I am so lazy here in Italy, I was jet lagged. I'm like, matt, just give me two papers. And this was one. 2020. What? Why the throwback?
- [40:05]
A
Because another paper came up that was about this topic and so that I dug into the literature. Like the one that came up recently was not that great, but this one, I was like, holy. I didn't know this. This is like super useful.
- [40:18]
B
All right, so that title, Pentoxifying for the Prevention of Post Surgical Keloid Recurrence by Andrea Tan et al. Apparently pentoxifying has been shown to inhibit collagen formation in keloids and square scleroderma and morphia in vitro, but I don't ever remember reading about that. So whatever. This was a retro works.
- [40:38]
C
You know how we use it in lipodermatic sclerosis. Sometimes I think it's because it's anti fibrotic.
- [40:44]
B
Maybe. Okay, maybe this was a retrospective study done at UT Southwestern. All patients had keloid surgery followed by Monthly intralesional injections of Tac 440 for six months. High risk group was also prescribed pentoxifying 400mg TID for six months. What made you high risk? The surgeon was like, you're probably gonna grow a keloid because it was based on previous, like, number of keloids you had and maybe history recurrence and maybe family history. But the surgeon just kind of said, you're high risk and then you're not. So 67 keloids from 45 patients were surgically excised. They didn't go into detail. There's like, was it sutured? Was it like a shave excision? Was it left to secondary intent? They didn't go into the surgical details at all. The paper and I just said that, was it shave? Was it elliptical, Was it left open heel? Okay, 39 keloids were considered high risk and 28 keloids were considered low risk. So the 39 keloids, those guys got the toxify filing and 28 didn't. And everybody got monthly inter interlesional tac 40. There was a third group of patients that kind of came about during the study. And these were the patients who the surgeon said, high risk, you're going to take pentoxy filine. And either they couldn't because, like, contraindicated pregnancy, bleeding disorder, whatever. And then there were also a few patients that couldn't take it for more than two weeks because they couldn't tolerate it. Which is kind of odd because doxy filing is like, like, I don't. Even if somebody said, well, what are the risks of this medication? I'm like, I, I don't know, I don't think there are any. So these were patients that were considered high risk, couldn't take it. So at the six month followup, there were 19 Keloids total in the high risk group that were left for analysis, 6 in the high risk control and 9 that were left in the low risk control. So, like half the keloids, like close to half of the keloids were lost to follow up. We have no idea what happened to them. So the authors calculated the percentage of recurrence using the denominator as the patients who weren't lost to follow up, which again was like close to half.
- [42:59]
C
This is study.
- [43:04]
B
So here are the numbers. The percentage of patients have keloids that recurred. The high risk control, 66.7. There were only like six people in that group. The low risk control, 22.2. They lost about 19 people to come up with that number. High risk treated, they lost about 14 people, but that was 10.5. So again if you just went on the numbers that the author said 66.7 recurrence in the high risk that didn't get the toxifying or couldn't tolerate it. The low risk control, the people that were low risk and didn't get any toxifying recurrence 22.22 and the high risk treated 10.5.
- [43:47]
C
And then the ones whose keela came back went to another dermatologist.
- [43:52]
B
Like the patients weren't randomized. Like if you look at the baseline differences, there are big differences like percentage of even men versus women and cheap, easy and safe.
- [44:05]
C
It's cheap.
- [44:06]
B
So I don't, I'm not going to suggest that people do this. I think a, a this is intriguing and I would say it's one of those studies where you say ha, let's do a better study and really see if this pans out. Because pentoxifying is just like the safest, easiest. It's like oxybuty. I'm giving my patients oxybuty and petoxifying because why not?
- [44:33]
A
You need to get them more X meds. So some oxybutynin, some toxifylane, more meds with X's in them.
- [44:42]
C
We'll do an episode meds with X in them.
- [44:45]
A
That'll be good.
- [44:47]
C
Now you know what I was thinking as I was perusing this article? Besides this is a crappy study. I was like, you know, all right, it is interesting. Like we do pentoxy filing in lipodermatosclerosis. And I was like well, well what if it's the anti fibrotic thing? And then I was like, what about like ccca, right? Like that is a disease where I, I think it is driven by inappropriate fibrosis.
- [45:14]
B
Could we try it there have higher rates of keloid formation. I don't know.
- [45:22]
A
But so the, well and let me throw in that the study that made me go back and, and search this up of, of pentoxylane and keloids. One just came out that was a trinetic study. So again now trinetics is too much in the, in the midst between. It could be low quality evidence, it could be decent evidence. I don't like that. I want just, I want it low quality with no question. But this study, they looked at people with coronary artery disease who were on patoxy filing versus you know, matched controls who had coronary artery disease who were not on Pentoxyphylline and looked at over a long, you know, fairly long period of follow up how many got, got diagnosed with a keloid and the ones who ran on pentoxy filing had a substantially lower probability of being diagnosed with a keloid while they were on the toxic filing. And so that was the, that's what made me be like well let's go look at the. So it's like now like in Matt Zyrus world where you've got, now we've got a meta analysis, we've got two studies looking at the toxify lead.
- [46:26]
C
We call that a data analysis. Oh, sorry, I'm on fire today.
- [46:34]
A
That is it, right? So we got two studies now that's enough. It's cheap, it's easy, it's a tough. Keloids are tough. I mean honestly, keloids are tough. It sucks, right? For anything.
- [46:46]
C
I hate kiloids.
- [46:47]
A
I like the ccc. I'm going to do some searching later to see if there's any low quality,
- [46:51]
C
anything associated with that. Maybe you could come up with that, you could do that trinetic study except you look at CCCA instead of keloids as your outcome.
- [47:02]
A
That seems. Yeah, I can see it, I can see it. All right, move on to my last one. This was a study looking at one of my favorite topics recently for some reason because they've been publishing, people have been publishing stuff about this more diaper dermatitis and. Right. I always like to talk about diaper dermatitis because every, you know, it's, it's not only can they come in to see us like you know, lots of us, we've, there'll be grandkids someday, there'll be kids, there's the whole thing. So this was the effect of open air of the effect of open to air frequency on diaper dermatitis recovery and maternal self efficacy in infants aged 0 to 3 months. A randomized controlled trial. So basically they took people who had mild diaper dermatitis, was done in Turkey and they randomized them to either get five minutes open to air every or six times a day or five minutes open to air 12 times a day. So either every two hours or every four hours they were open to air for five minutes and just kind of, you know, lying there with a little push, a little, you know, some little something over there so if they pee it doesn't go everywhere. And it made a. And there was no other therapy. So they didn't do any zinc oxide, they didn't do any like Literally nothing else. It was just every two hours or every four hours. And the kids who they changed the diaper every two hours got better. They resolved completely in less than two days. And the kids who they did every four hours, it took over three days. So like three and a quarter on average. So it made a meaningful difference. The other thing that was interesting, they had a, was a maternal self efficacy score, which I think was the basically like a do you. Do you feel like you're a good mother? Score. But it was a real, like, there were 10 questions and whatever and blah, blah, blah. But the ones who got randomized to the every two hours and they did do like an hour long training with them of like, here, diaper dermatitis and here's how you change a diaper and the whole thing so that they, you know, set the standards. The ones who got the every two hours compared to every four hours had a more significant increase in maternal efficacy score, self efficacy score, where they, you know, felt better about their mothering.
- [49:31]
C
Okay, is this open to air or is this just not sitting in your pee in your wet diaper?
- [49:36]
A
Could, could be either. But the. So the main. Right. But it gives us a. Because this has actually not really been studied before. So it's a, you know, it's a standard recommendation that whenever your kid has diaper dermatitis, you know, frequent diaper change is open to air, but it's never really been studied. And so this was the, the first, you know, you got to randomly, you got to choose some kind of control group. So they choose. Chose every four hours. So it now gives a very solid thing to be able to tell people, hey, there's a good study that showed if you, you know, do a diaper change every two hours, leave them open to air for like five minutes, take the diaper off, wipe them down, just let it, you know, let the baby be kind of naked for five minutes, then put the new diaper on, do that every two hours. That works better than every four hours.
- [50:23]
C
I bet they just. I would let them run around naked outside. That would have been how I would have been.
- [50:27]
A
They were zero to three months old.
- [50:30]
C
Okay, never mind.
- [50:32]
A
Yeah. What kind of a mother are you?
- [50:33]
C
My kids are running around three months about yours.
- [50:36]
B
I. So did they allow, like, what if the child had a horrible accident? You'd be like, well, you got three more hours. I need to follow protocol.
- [50:48]
A
Yeah, I.
- [50:48]
B
Sorry.
- [50:49]
A
I think they were allowed to change in between. I think they were allowed to change in between.
- [50:54]
B
Well, then how did they control for
- [50:56]
A
who Was because whenever they change in between, they didn't leave open for five, five minutes.
- [50:59]
B
Oh, they didn't leave it open. So the, the open air was right. And, and put, and put it right back on.
- [51:04]
C
They didn't randomize to like change the diaper really quick versus leave them open for five. Like you're on the Q4 hour. I don't know. You know what? I think it's just the more frequent diaper change. My kids like, because I worked my whole life when my kids were little, so my kids were always in daycare and daycare is like, you know, they are, they have strict rules, right? Like if I were with them and be like, hey, you peed, but we're at the store and like, you know, we're gonna hang out or whatever, I'm too lazy to go do it. But like they had a log and they had to have their diaper changed. It was every two or three hours. I can't remember. They had to mark it off in a log. They could never go more than three hours out of diaper. My kids never had a diaper rack.
- [51:46]
B
I think I only would change my kid when it was like poop. Cuz you would smell it and you'd be like, oh, I need to change you. I don't think I ever thought, hey, they may have peed time to change a diaper. My kids had diaper dermatitis like all throughout their babyhood.
- [52:02]
A
Things are, it's all coming together.
- [52:04]
C
It's all coming together.
- [52:06]
A
All coming together.
- [52:06]
B
They resent me now and they, they don't talk to me anymore. That's all.
- [52:11]
C
Yeah, I think my kids never had diaper rash and it was. I do attribute it to the frequent diaper changing that they received primarily at daycare. Maybe somewhat with me.
- [52:22]
A
Ferris, I know we've talked about this before. Did you have any kids during. Did you ever have any pregnancy? You had a kid during residency, right?
- [52:27]
C
Are you effing kidding me? You're asking me this question? Do you not let me. I'm just going to share my experience of my having a kid during residency.
- [52:35]
B
She came in on fire.
- [52:41]
C
Intern, I emailed you. Dear Dr. Zyrus, my chief resident, I wanted to let you know that I am pregnant. I am due in December of my first year. Dear Dr. Ferris, that's great news. You six weeks of time away from residency. That will be all of your vacation, all of your cme.
- [53:03]
A
That's right.
- [53:04]
C
And all of your maternity leave. I was like, okay, so yeah, I took no CME, no vacation. I worked Saturday MO's in case I needed a C section. I. And I had my six weeks of maternity leave and then I came right back.
- [53:18]
A
Yep. See, that's. I should have made you work extra.
- [53:21]
C
I can't believe you don't remember this. I. It's like, amazing. I'm still. I'm friends with you at this point.
- [53:25]
B
I have.
- [53:26]
A
It's. What? It's one of my strengths and weaknesses. I have no memory for episodes. Like what. What actually happened in my life? I have no idea at all. I can remember all kinds of stuff that I've read. Like what. What happens? No idea. None. Like, pictures don't help. I can't remember anything. I see the picture. Oh, that looks like it was fun. Yeah.
- [53:46]
C
Yeah. Okay. Well, yeah. Yes, I did. I had one child, and then I had my son when I started my two plus two year.
- [53:55]
A
Okay.
- [53:56]
C
Like, so. Yes, that was okay. I had him and then I would bring him in the lab with me, and I went back to work at two weeks after my son at six weeks off with my daughter. And then. Well, my first one, I had like six weeks. Then six weeks and then about two weeks. It's a different world.
- [54:14]
A
It was. It was a different world. It's very true. All right, well, that's. That's it for this week. I want to thank everybody for joining us. We hope you laughed a few times. We hope you learned a few things, but mostly we hope you're planning to join us next week. Until then, I'm Matt Zyrus.
- [54:30]
B
I'm Tim Patton.
- [54:31]
C
And I'm Laura Faris. And we are Derms on drugs.