← Derms on Drugs
Derms on Drugs
Breaking Dermatology Literature: A Probiotic for AD, A JAK Inhibitor for Pemphigoid & IL-23 Inhibitors for Guttate Psoriasis
01:00:33
Loading summary
Transcript211 lines
- [00:11]
A
Welcome to season two of Derms on Drugs, a video podcast brought to you by Scholars in Medicine. The best educational platform in dermatology and provided at no cost to medical providers, Derms on Drugs is where cutting edge derm meets hit or miss comedy. I'm Matt Zyrus, and each week I'm joined by my residency buddies, Drs. Laura Faris and and Tim Patton, to use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of dermatology and you'll actually have fun listening. New episodes drop every Friday on Scholars in Medicine, Apple Podcasts, Spotify and other major podcast platforms. And as a reminder, the video component has some of the key figures and tables from the articles we talk about every week. So this week you're in for a special treat. We've got another one of our patented six pack episodes where we are going to talk about the things that have grabbed us as most interesting in the literature recently. A bit of a potpourri, if you might say. Dr. Farris, go ahead and get us started. What do you got?
- [01:14]
B
All right, so I'm going to start off with something about psoriasis.
- [01:20]
A
By the way, I have to let all of our listeners know how much Pat and Farish roll their eyes while I'm doing the intro.
- [01:26]
B
All right, I think if you watch, that's another reason to watch the video portion so you can actually really appreciate that in its full glory. Okay, so speaking of glory, this is in the unproofed glory straight out of the jad. So the paper that I picked was sustained remission of gutate psoriasis flares with short term IL23 inhibition, a case series by Hodelin et al. So case series 9 patients with who had flaring gut Tate psoriasis. So these were patients. Two of them had a history of plaque type psoriasis, the other seven did not. And of eight of the nine had been tested for antistre and otiders and eight and all of them happened to be positive. So just to give you a flavor of who's in there, one of the plaque type psoriasis patients was actually on OTESLA when they had their flare. So all these patients were started on Skyrizi on average about two months into their flare. Sometimes it was as quick. The earliest was started two weeks in, sometimes as late as six months. Most of them were also using topical steroid. So how do these patients do? So all nine of them went into remission after just two or three shots of Skyrizi and only one recurred and that was 16 months later. And quite unfortunately after another strep infection. For everyone else, remission was pretty impressive. So they were, you know, duration of follow up was like 11 months off drug and people stayed in remission. So why is this interesting? If you are a Skyrizi Aisle 23 clinical trials aficionado, you might have heard of the knockout study if you was like presented at aed, if you go to H, you know, these like, like HCP live type things. Like you can see Andy Blauvelt talking about it. So this was a randomized phase two trial where they basically said, what if you have patients with psoriasis and you like give them early high dose skyrizi? So like 300 or 600 milligrams per dose at week 0, 4 and 16. And what they found was that, you know, patients had this high response rate when they looked in their skin that knocked out their tissue resonant memory T cells. And so they, you know, the theory, they theorize that aisle 23 is important for knocking out memory T cells in the skin and maybe we could actually like knock out psoriasis. So I thought this was interesting. You know, this was, it makes me think like maybe if you're going to pick a biologic to hit a new gutate psoriasis patient with, go with skyrizi or an IL23 inhibitor mechanism, kind of makes sense. And you know, maybe this is going to change how we think about treating psoriasis. Like should we be starting with IL23s? You know, these are like, it's a proof of concept, it's sort of hypothesis generating. It's not a randomized clinical trial. But I thought something helpful.
- [04:38]
A
All right, two quick questions here, Ferris. So number one, do you check, and we've talked about this before on derms and drugs, but gutate psoriasis is common. Do you check an ASO titer in all of your gutate psoriasis people or do you just put them on some amoxicillin or penicillin or do you not. Do you do neither?
- [04:56]
B
Yeah, I mean if they have evidence of strep infection, like I have a strep, I have a really sore throat, I will get them tested. I don't test for the antibodies and I will of course treat anything that is true strep. I don't prophylactically test. I do feel like it's rare that I get the brand new Gutate psoriasis patients, but I don't. How about you guys?
- [05:21]
A
Patton?
- [05:23]
C
I don't chase symptoms. Not. I don't randomly order the antibody.
- [05:27]
A
I take the titer so far is not. Technically, this is off label use of Skyrizi. Correct. It is only approved for.
- [05:33]
B
It is not FDA approved for the treatment of guttate psoriasis. And these people, plaque type psoriasis and psoriatic arthritis. But we love off label treatments on derms, on drugs.
- [05:45]
C
So I think I would try and get this covered. Insurance would say no and they'd say, you have to do this and I would do that and then I would say that didn't work. And then like guttate psoriasis would go away and then I would get the Skyrizi approved and they'd be like, that's all gone now.
- [06:02]
B
Then you'd have it in your refrigerator and you could use it in the next person.
- [06:06]
C
I do have a lot of samples.
- [06:07]
B
Samples, yeah.
- [06:09]
C
Don't tell anyone, okay?
- [06:11]
B
I know.
- [06:12]
C
It's just between us academic so, so.
- [06:16]
B
Interesting our thousands of listeners.
- [06:18]
A
So two or three, two or three doses of Skyrizi and their gutate psoriasis was cured, at least for the short term.
- [06:26]
B
Until they got strep again.
- [06:27]
A
But yes, until they got strep again. Okay, well that's cool. That's. That, that's a good one, Ferris. All right. That's better than your usual like smart person stuff I'm never gonna see in clinic.
- [06:41]
C
Okay, that's real shade right there. As the kids say these days, throwing shade at Ferris, Earl.
- [06:50]
A
All right, Pat, what do you got?
- [06:52]
C
All right, I did an article from the June 2025 issue of the Journal of the European Academy of Dermatology and Venerealogy titled Digital Dermoscopy. Follow up for Acquired longitudinal Melano nychia by Moscarella et al. Some quick facts about nail unit melanoma for our listeners. It accounts for 1 to 3% of all melanomas worldwide. Absolute incidence is actually the same across all races. There's a higher relative rate for non Caucasian populations. More often affects the fingers than the toes. Most often affected digit. You guys got a guess?
- [07:28]
A
Thumb.
- [07:29]
B
Thumb.
- [07:30]
C
It's a thumb. There's actually a different ABC mnemonic for nail unit melanoma. So for A, they say age, it's peak incidence between the 5th and 7th African Americans, Asians, Native Americans, higher relative rate. B is brown, black discoloration, breadth of 3 millimeters, variegated B borders. So C is change in nail band or lack of change in nail morphology despite treatment. So if you think it's fungus and you treat it for fungus and the pigment doesn't go away, then you start to think about melanoma. The D is the digit affected thumb number one, number two, index finger number three, great toe. E is extension of pigments. So that's Hutchinson sign. And F is family or personal history of melanoma. So a little bit of a different mnemonic I thought was always kind of cool. There's also dermatoscopic criteria for early nail unit melanoma. Involvement of more than two thirds of the nail. Brown, black background, blurred borders, irregular lines, granular pigmentation and or nail dystrophy usually presents as longitudinal melanychia, which is the most challenging aspect of nail unit melanoma, because way more often than not it is benign. Longitudinal melanicia is benign. And performing a biopsy isn't like performing a biopsy. Pigmented lesions, technically hard to do. It can permanently damage the nail. It's just like, I don't want to do this. So the goal of this paper was to see if there were any dramatoscopic changes, changes that could be used to determine which longitudinal melanic it could be followed clinically, which changes should prompt a biopsy. Multi center retrospective study. Patients had a pigmented band and were followed for at least one year and eventually had a biopsy of the band performed. Well, some of them did. So final analysis included 62 bands, 56 benign bands, and six malignant bands. 27 biopsies were performed. That's what picked up the six melanomas. So, you know, most lesions, again, like, were benign. The. All of the six lesions that were biopsied were malignant melanoma in situ. First table looked at the baseline characteristics of the bands.
- [09:29]
A
Did they. So they, they didn't biopsy all 56. So this.
- [09:33]
C
No. 27 biopsies. Yeah, 27 biopsies were done.
- [09:38]
A
Seven biopsies. So 27 biopsies were malignant. So it's possible. Wait, did you, I'm sorry, did you say seven biopsies total?
- [09:47]
C
27.
- [09:47]
A
27. Okay, so 21 benign biopsies. Okay, so that's good. I thought they biopsied, like, none of the benign ones, which I was like, well, how do they know they were benign? But okay.
- [09:59]
C
I mean, they still don't know that, right?
- [10:00]
A
Yeah.
- [10:00]
C
So they're, they're saying they're in, in their benign analysis, they're including things that weren't biopsied, so who knows? But first table looked at baseline Characteristics. So this was kind of a, what can I use at baseline that would, you know, that differentiates malignant from benign? And there was nothing. Right. So width of the band, color, granular pigmentation, irregularity, hutchinson sign, nail dystrophy. No statistically significant differences between the two groups. After a median follow up of 17 months, 27 bands underwent biopsy. Six melanomas, all in situ. What dermatoscopic changes occurred more often in the melanomas? If you had an increase in the number of colors, appearance of granular pigmentation and an increased intensity of pigmentation, and they have some examples of it, we can put those up on the, on the podcast. Those three things again. Number, increase in number of colors, appearance of granular pigmentation, and an increased intensity of pigmentation. Statistically significantly different between benign and malignant legions. Enlargement occurred in 50% of melanomas and only 23% of benign lesions. But that wasn't statistically significant, so that alone didn't help you. Like I said, they have some photos there. My takeaway is that if you're not really sure if longitudinal melania nicche is benign or not, it's reasonable to take a dermatoscopic image, have the patients come back three to six months, compare baseline follow up dermatoscopic images. You see any of those changes that they mentioned, go ahead, do the biopsy. You know, I think most of us have dermatoscopes. Capturing images can be a little bit tricky, but it's not like, too technically challenging. You can get pretty good dermatoscopic images with your cell phone and a dermatoscope. If the baseline and follow up images are stable, I think it's okay to clinically follow. Some interesting points about the paper were raised in a letter to the editor about the article. One point raised, two lesions were diagnosed around five years after initial presentation. Another lesion was stable for one to two years before changes were noticed. So how long do you need to keep coming back? You know, I used to think like, oh, come back in three months. Nothing changed. This is therefore not melanoma. But it did take longer for one of the particular lesions to undergo that change. So, like, what do we tell patients? Two years is your cutoff? No changes in two years. I, you know, just kind of, I think I will definitely be doing this. It'd be nice to have a baseline difference where you could say, because of these features, half of the melanomas involved less than one third of the nail plate. So over reliance on bandwidth should be discouraged. A big Drawback to the study was this was all a bunch of white Italian people, you know, so skin of color. It would have been nice to see if they have similar sort of things that you can follow that that would make you think more about biopsy to rule out melanoma.
- [12:48]
A
All right, so do you think so first increase in the number of colors. I don't know if that's, that's like a pretty. So what did like, was that like.
- [13:01]
B
Different subject on like dermoscopy. And again, they have photos of all these. It's not like, oh, maybe that increase. Like it's with photographic monitoring.
- [13:11]
C
It's like. So you know the examples they gave you look at the baseline. It's like, all right, three, there's kind of three little medium brown lines that are there. And then in one example where the patient didn't come back for five years, which was great, they, they missed all their appointments but came back in five years. And you know, now you had that medium brown and some light brown and some dark brown. And you know, it's like, how many different colors were there at baseline? How many different colors were there on follow up? Yeah, fine. A little bit subjective, but not terribly so. Right.
- [13:47]
B
And I mean, like, that's the beauty of having the photos. You can go, all right, that's like change. That's, you know, you're not trying to say, well, there was only light brown, but now there's light and dark and medium brown. Like, you know, trying to do it descriptively would be hard, but with photos, I think it's doable. That's. I photograph these and that's what I do. I mean, if I know it's melanoma, I biopsy it, but I photograph them because it is kind of morbid to get a nail biopsy. And I hate doing them. It just isn't the reason.
- [14:17]
C
I mean, technically hard. I been doing it for how many years? I mean, the problem is, is we don't do it a lot. So I just don't have that same level of surgical confidence going in there.
- [14:28]
A
Yeah, yeah.
- [14:29]
B
And then the other thing I thought was interesting is that, you know, like you, we all see pigmented nail bands that were like, that's fine, you don't take a photo. None of those would have made the study. Right. They only did it in cases where they had at least two photos and some clinical follow up. So if you. They're not looking at the ones that we just dismiss outright. So these are sort of the more challenging ones.
- [14:49]
A
Well, I would say when I look at the pictures in this. The what? The two that were melanomas that they took pictures of or at least melanomas in situ. Like the sec. The, the baseline pictures. Maybe I would have, maybe I wouldn't have. But like the, the follow up one where they did the biopsy though, both of those, I'm like, well, yeah, I would have biopsied that.
- [15:12]
C
So dramatically different. Yeah, right.
- [15:14]
A
I wouldn't, I would. Didn't need the baseline to be like, that one's pretty scary. Like, whereas the normal ones look pretty normal. Like, I just, I'm not. This didn't convince me that you need the, the pictures didn't convince me that you need the dermoscopy.
- [15:30]
C
So you're saying if you saw them at that second follow up, that would be enough. Like I'm, I'm doing the biopsy.
- [15:37]
A
Well, at least I'm sending them to somebody to do a biopsy or, you know, they're not Your run of the mill longitudinal melanin nicias is what is, I guess what I would say.
- [15:51]
B
But we're not seeing every photo in this study. Right. Like, we're not seeing every one of them and you're seeing the ones that are the best quality photo and maybe the best examples. And so.
- [16:01]
C
And I think the point is that with the melanomas, when you look at the baseline, I don't think I would have biopsied. I mean, it was only the two examples. I wouldn't have biopsied either of those at the baseline one. That's the whole point.
- [16:11]
A
Yeah, I definitely wouldn't have biopsied. Figure 3. Figure 2, maybe, but probably not.
- [16:17]
C
Yeah. So I think that's the point is this is probably the best way to manage these patients. Unless. Right. You think, oh, this is really bad at that first visit.
- [16:26]
A
Right. So again, how long did you guys say you would probably separate them by? A year? Six months.
- [16:31]
B
Six months for me. That's usually what I say. And I, I mean, I always say to the patient, like, I oftentimes will say, like, take a picture, I'll take it with your phone and if it changes earlier, call me. Like, I'll get you in. But I, I can't even remember anybody ever being like, oh, I swear it's changing. And then having them come back. I say six months.
- [16:51]
C
Yeah, that's a good. I have no idea. I think I probably have said three.
- [16:55]
A
Okay.
- [16:56]
C
Okay.
- [16:57]
B
The other, like little pearl for nail unit melanoma is that there is an association with trauma in developing melanoma in that nail. So, like, I had a patient who's like, oh, this is my nail, but it only looks like this because my bird bit it. And I was like, that's kind of crazy. That's not true. But then it actually. When I read up on it, there is actually an association. There's a higher risk of developing what? That maybe that's not. That's too strong. There is an association between trauma to the nail and subsequent nail unit melanoma. So keep that in mind.
- [17:29]
A
So basically, it's. If they say trauma, don't automatically be like, but. Yeah, because. Yeah. And I think I remember that. But the big thing with trauma is how long ago did it happen? So are you looking at blood or are you looking at pigment? Which usually is pretty easy to tell.
- [17:47]
B
So a week ago, I'm gonna think it's blood. But, you know, if it was a couple years ago, just, you know, don't. Don't do what I did and dismiss it outright as not being associated because there actually is the association.
- [17:59]
A
Okay.
- [17:59]
C
I say Bob Marley never worried about his melanoma because he was like, ah, I injured that playing soccer. I remember.
- [18:05]
B
Yeah. Yeah. I. It was. Bob Marley was not the person I told that to. I just want to put that out there.
- [18:11]
C
Good. Yeah.
- [18:13]
A
Good for you.
- [18:14]
C
You haven't been practicing that long, I guess.
- [18:16]
A
Yeah, good for you. All right, so let's jump into mine. And as listeners from our last episode may recall, I am now doing a little something different for our six packs. And I'm going to be doing a little potpourri of my own of, like, three very quick hitter articles. Because I'm kind of a believer if I can't summarize the article in, like, 15 to 30 seconds, it probably was too complicated to be clinically useful. So number one, if you could actually.
- [18:46]
B
Summarize anything in 15 seconds, I will be amazed. And I'll also.
- [18:51]
C
Ever happen.
- [18:52]
A
Yeah.
- [18:52]
B
Cut you off from 12 or 14. So let's see how this goes. Give it a whirl.
- [18:58]
A
So first, this was an article from Journal of the European Academy of Dermatology. Venerealogy, efficacy and safety of. So first. My first three year Atopic dermatitis Focused efficacy and safety of lebricizumab and atopic dermatitis over 24 weeks and analysis from the BIOREP registry. Here is what was interesting here. They looked at people who are bio naive versus people who had failed Dupy or people who had failed Jack had inadequate response. Response to one of those. And those people still did well, but they did not do as well as people who had not previously failed one of the other two drugs. So the. And one of the interesting things, if we look at a low endpoint like easy 50, then it didn't seem to make much of a difference. But if we got up to things like Easy 75 or Easy 90, then it was a bigger difference of that the people who previously failed DUPY or a Jack didn't do as well. They. They may have caught up some at a longer follow up point week 24, but looked like there was a lot of dropouts. So hard to know. But basically confirms for us kind of what you know, we would. You would expect that people who fail one systemic agent are a little more recalcitrant to, you know, something else that does something similar, you know, anything. Any comments from the two of you on this one?
- [20:31]
B
Well, fits with every other psoriasis or whatever type study. Yes. You're selecting for patients with refractory harder to treat disease.
- [20:40]
A
Yeah.
- [20:41]
C
Better response in naive individuals.
- [20:44]
A
And it is interesting, we do have some data that suggests that inadequate DUPY responders do not have a reduced response to jaks. So that. Which kind of makes some sense because if you didn't respond to doopie, maybe it was a different pathway than IL13 and JAX hit a bunch of pathways. So it does make some sense to me that though now that if I've got somebody who failed dupy, I'm probably less likely to go to Trello or Libry than I am to go to a Jack or to Nemo. And that again fits. We don't have a ton of data for that, but it kind of fits with our. With the experience for psoriasis. All right, number two for me. So as lots of people may know, I am. Well, let's. I'm a kind of believer that the conjunctivitis with Dupy and other IL13 inhibitors, there's some belief that maybe it's an immune shift, some belief that it's more the goblet cells. I believe more the goblet cell hypothesis. But the interesting thing here, large series of people who got it. And again, no real easily identifiable risk factors. But the big thing was this was people who with doopie got it earlier, I'm sorry, got it later than people who got it on Trello. But it was probably worse in the people who got doopie because more of them. So a quarter of the DUPY patients ended up DCing because of it compared to 15% of the Tralo patients who got it you know, hard to know if that's really meaningful. But the most interesting thing was that they had a bunch of people who switched from DUPY to Trelo and a few people who switched from TRELO to dupy. And so even some people who switched from DUPY to Lebri or Trello to Lebri. And no matter what, every single patient improved some. So the conjunctivitis was not as bad after they switched drugs. Maybe that was just, you know, tincture of time. But that was interesting that if you do get conjunctivitis on an IL13 inhibitor, switching to another IL13, if patient's like doing great but has conjunctivitis, it tells me it does make some sense and reasonableness to try switching to a different IL13. So they'll probably continue to do well, and there's a good chance surgic divitis will improve. But it's hard to understand why that would happen. You know, that's the kind of takeaway.
- [23:16]
C
There are there huge differences in the percentages between the 413 combo, like Doopie versus just the 13 blockers, in the percentage of patients with conjunctivitis.
- [23:27]
A
It's maybe a hair more common in dupy, but that's not like, we don't, we don't really know because it's, it's hard, right? The doopie patients, the baseline DUPY patients, were so different from the patients in any other atopic dermatitis trial. So it's, we don't know is the big takeaway. And then number three was a new probiotic study that literally, well, I don't want to say literally, if almost literally, knocked my socks off. So figuratively, title of this study, Transforming atopic dermatitis management Probiotics is a game changer in immune modulation. A double blind placebo controlled clinical trial. This was out of Italy. Well done study. Not a huge number of patients in it, but I think There were like 60 patients, roughly 80 patients in here. So randomized, double blind placebo controlled. They were allowed to use topical steroids. It was nuts how well this worked. I mean, just kind of nuts. So the, the decrease in the score ad and these objective measures was like big, like big, big. So it was really an interesting thing. Let me find the exact numbers here. So the exact numbers. So there was. In the score ad, the people who got the probiotic had an average decrease of 20, roughly 25. And the people who got the placebo had a decrease of 5 points. Even more telling, easy scores, the people who got the drug had a mean reduction of 13.7 points. Not the drug, the probiotic. The people who got the placebo got a mean reduction easy score of 3.1. And these were patients who, you know, the baseline easy scores were in the low 20s, so 23, 24. And so these were like clinical trial severity patients. And they got a lot better on this probiotic. Now, with probiotics, you gotta talk about the specific probiotic. And so this was a probiotic that is available in Italy, but it is specifically available in the U.S. it's called VIS biome V I S B I O M E and it costs about 70 bucks a month. Now the probiotic that I've always.
- [25:58]
B
It's an oral probiotic. An oral probiotic, One of those topical.
- [26:03]
A
Okay. Nope, nope, nope. Take it. VIS Biome V I S B I O M E and it's marketed more for GI disease, but 70 bucks a month. So expensive but not terrible for something that's got really strong data. Now the, the probiotic I've always recommended is called Now Probiotic 10. And it has seven. So there's eight strains in this Vizbiome or not seven? There's eight species in it. The Now Probiotic has seven of the eight species. But that doesn't mean that it's definitely the, you know, it doesn't. I, I can't sit here and say, well, the now probiotic works just as well, but if the $70 cost is an issue, then the now probiotic is like 8 or $9 a month. I would say I haven't seen this kind of a result with NOW Probiotic. I wouldn't have said it was going to be that big of a difference. But this Visbiome randomized double blind placebo controlled trial, used it with topical steroids. A very reasonable thing now in my mind to offer to people who really don't want to do a drug or do it together with a drug. Because we know that probiotics really have a lot of immunomodulating effects. Thoughts, anything that, that like, really like. What do you think?
- [27:24]
B
I mean, I love the idea of it working. I do think like microbiome probably is. I used to kind of think it was baloney, but now I think it probably does matter for a lot of diseases. So, yeah, I mean, people would love that. So how do you buy this stuff? Is it like you got to order it online?
- [27:45]
A
You ordered, you ordered online this vizbiome again? Viom they fund the study? I don't know. You know, I looked through the whole thing. I couldn't find, I've been, It's, Yeah.
- [27:59]
C
It's not believable, right? I mean, I'm not saying, oh, this. It's just that atopic derm is so hard to treat. We didn't know what to do before we, you know, got these doopie in the Trelo and the JACK inhibitors and all those guys. And now we're supposed to believe that. Oh yeah, this probiotic totally, like, it'll totally make your, it's, I, I, this is one of those. I would have to see it in like 10 patients before I'd be really convinced that yes, this actually works.
- [28:27]
B
And it was randomized, right? Or like it was randomized blinded.
- [28:31]
A
Randomized double blind placebo controlled, like.
- [28:35]
B
Oh yeah.
- [28:35]
C
Which, I mean, like what did they make up the data? I don't believe they did that.
- [28:39]
B
And the steroid, the steroid was like investigators choice, patient's choice. Or it, like, it wasn't like the, the microbiome group got clobazole and then the other group got hydrocortisone.
- [28:49]
A
No, no, no. The two steroids that they used were either hydrocortisone, butyrate or mometasone. Those were the two possibilities. And the other thing that I don't, I'm looking to see if I, I don't remember being able to find it 60 days. So they gave this two months. So totally a reasonable thing to do if you got somebody who doesn't want to do a drug or if you want to try and save money, you know. But even for your mild atopic derm patients, this now makes tons of sense. But it, it, it was, it's hard to believe, but you know, there's now a lot of data around the basic science of probiotics in atopic dermatitis. Like a lot of, a lot of data around it. And now this really supports that the right probiotic seems like it could make a huge difference. Move on to our next study. Ferris, what do you got?
- [29:40]
B
I have red light PDT with 10% ala gel for superficial basal cell carcinomas, a randomized vehicle control double blind multicenter phase three study. Todd Schlesinger et al. Okay, so this study looked at 10% ALA gel and red light PDT and 187 patients randomized 4 to 1 to either get the ALA or vehicle placebo. So you know, I kind of like it. Like you get actually randomized to, you know, is this ALA or not? Multi center study. So this is like, you know, legit study design. Everybody had biopsy Proven treatment, naive, superficial bcc, mostly trunk and extremities.
- [30:27]
A
I do want to say the title is a little. They're kind of lying in the title. Right? So is maybe they tried for this to be double blinded, but it like people knew which, which one they got, right? They had.
- [30:40]
B
Because it hurts more.
- [30:41]
A
Yeah, because, you know, if you get the ala, it hurts and if you didn't get the ala, it didn't hurt. So it wasn't really double blinded. It. I probably would have called this.
- [30:49]
B
You can have like. Okay, it's at least single blinded.
- [30:53]
A
Yes.
- [30:55]
B
Okay, so patients got two cycles of pdt. So a cycle is two PDT sessions a week or two apart. And then the target lesion was surgically excised at 12 weeks. So it wasn't like, say you have histology. So what were the results? Clinical clearance after the last PDT cycle was 83% with the ALA gel versus 21% with vehicle histologic clearance, 76% versus 19%. So that's, you know, that's significant. And you know, the other reason why I like that is we all know like a lot of BCCs just go away after you biopsy them. So, you know, there's studies where you don't have a control arb and it's like, oh, look, we treated it and like we have a curated 90%. I'm like, well, what was your cure rate with biopsy? So now we know the curate with biopsy wasn't like, it wasn't just a biopsy response. And then composite endpoint, which is clinical and histologic clearance, 66% in the ALA arm. 89% of patients in the ALA treated arm had the investigator rated as very good or good cosmesis. 95% of patients said they do it again. It was the typical side effects of like, you know, local reactions, redness, pris, pain. And the mean pain score was 4 out of 10. So, you know, how does this stack up to the other modalities? We have surgical excision, you know, five 95 to 99%, five year recurrence, freeze survival or recurrence free. I guess survival is still the word and you know, but more scarring. Mohs, 99% cure rate, you know, imiquimod 5 fu, 80 to 85%. So, you know, I, I thought this was interesting. It was nice to have sort of a more rigorous controlled study. So is it revolutionized what we're going to do? No, but, you know, I thought it was interesting. It's an, It's It's a name, you know, it's a, an option you can give to patients. Now, I would still argue like ED and C is kind of up there with that curate and is a one and done thing, although maybe cosmetically not quite, quite as, not as effective.
- [33:18]
A
So the big benefits, so the big thing here is you're getting a, might take away a lower cure rate than say, ED and C or surgery in exchange for a better cosmetic outcome. If you cure it, if you were to compare it to say, a miquimod, you're getting less, you know, time of, you know, having the wound and all that kind of stuff.
- [33:48]
B
You could treat multiple, right? Like a lot of times people have, like, oh, they've got a bunch of superficial BCCs on their back. So you could imagine, like you could treat multiple lesions at once and be done. Not that you can't do that with ED and C, but, you know.
- [34:03]
A
Okay. All right, Pat, what do you think you're gonna start? What is this?
- [34:07]
C
I thought this was, I thought this was terrible. I, I thought this was like, just, I think this is a bad treatment. I think it's inconvenient for the patient. I think they tried to make it sound as good as they possibly could because it was funded by the company that either makes ALA or makes the light unit or maybe makes both. I don't know, but everybody involved, well, well, they were clinical trial, but it was, you know, four authors worked for the actual company, four or five authors in the abstract, they, they didn't even talk about histologic clearance in the abstract. Is that insane? Since when do we treat cancer and say, well, clinically looked like it was gone? Like histologic clearance is the gold, is the gold standard?
- [34:55]
B
I, I, I mean, do you look for histologic clearance after you do an ednc? I don't, I'm looking.
- [35:00]
C
It doesn't matter if you want to look at it, the effectiveness of a new drug or whatever. Not, maybe not a new drug, but if you want to look at the effectiveness of a drug in the treatment of skin cancer, you don't put out a study that says clinically they look like it was gone. Like, clinically it looked like she didn't have syphilis. Like, get out of here.
- [35:19]
A
Just to, to note, Patton is not talking about Ferris.
- [35:22]
B
All right, thank you, I appreciate that.
- [35:24]
C
And I don't, I, I, I, you know, you know how I feel about these pharma funded studies. I think this, this just really irritated.
- [35:34]
B
Me in many different ways to do these kinds of Studies, unless they are funded by the company that is going to.
- [35:40]
C
That's fine, but they should be very, very honest. That look, this wasn't that good. And it's actually more inconvenient for the patient. You call up a patient with a superficial basal carcinoma, hey, go pick, Go to the store, go to the pharmacy, pick up your Fidex, use it twice a day for four weeks. You don't have to come back here, you don't have to degrease it. We don't have to sit there and like scrape it because they did like debride each lesion. And then we're going to put this on and then you have to hang out for three and a half to four hours and then you come back and the light's going to hurt.
- [36:08]
B
But they also have like, you know, field, like, you know, field cancerization. Right. So the way that I would see this is in the person who has a bunch of, you know, AKs, a bunch of st. You know, I want to do a field therapy. This is an option. And there are patients who like pdt. I mean, I see them and they're like, yeah, I like that pdt. I do not like that Effudex cream you give me. So if I could say, like, kill two bird. Sorry, feed two birds with one scone. That's how we say things in academia now, because we don't kill birds, but we only feed them, so we're harmed in the making.
- [36:49]
A
What did you say, Ferris? If you could feed two birds with one seed.
- [36:53]
B
No, one. A scone.
- [36:56]
C
A scone.
- [36:57]
A
Oh, okay.
- [36:58]
C
Like a muffin.
- [36:59]
A
Okay.
- [37:00]
B
Yeah. So, you know, you get field treatment. You get treatment of your, of your BCCs. I, I think it's not a. It's a good number to have to know. And I, I guess what I don't love is a lot of times when you have like clinical clearance or an open or maybe histologic clearance is done in most studies. But, but like a lot of times these, like cancer therapy, you know, basal cell treatments, it's like a single. Right. It is. There's. It's not randomized to anything. It's a single arm study. And as we know based on actually studies we did at Pittsburgh, biopsy gets rid of a lot of basal cells. And I think like most, most surgeons would say that for low risk skin cancers, a lot of times you go in and there is no visible tumor. So, you know, they actually did it the right way.
- [37:51]
C
Right.
- [37:52]
B
And they didn't take a bunch of stuff that had already been biopsied off.
- [37:55]
C
No. And I think the biopsies specifically, they said like a little 3 millimeter punch. Like I don't expect that to actually clear a right basal cell shaving. Yes. Or. Yeah, they did it in a specific way. So. Yes. Fine design, but the numbers aren't good. I. I guess I'm just not a huge PDD fan and I was going through NCCN guidelines, you know. So the NCCN guidelines for field cancerization, they actually say 5fu is the preferred treatment and they actually like adding the calcipatrine to it. Now for superficial basal cell carcinoma, they actually say amiquimod is the preferred therapy for superficial basal. And that's, that's probably my least favorite treatment.
- [38:36]
B
It is my least favorite treatment too. So, you know, if this were squam in situ, I would be like, I know that that's not going to be my, you know, PDT is not my choice. But superficial basal cells don't do that well with, you know, I, I think with either imiquimod or 5 fu.
- [38:51]
C
Oh my gosh. Works great for 5 fu and there's data to back that up.
- [38:55]
B
Really? Yeah. I feel like squames in situ do better with the combination.
- [39:01]
C
There was a head to head study of 5 Fu, Mal PDT, amiquimod. And amiquimod was superior to Mal PDT. I think that's why it got the NCCN guidelines like gold star recommendation. And topical 5 fu was non inferior to Mal PBT.
- [39:18]
A
Remind me, by the way, what's the brand name of the MAO drug?
- [39:24]
B
Is that Amalas? Amaloos.
- [39:26]
A
Amaloos. Is this the bio. Is it Biofrontera or who's. Do you know the company?
- [39:31]
C
Yeah, yeah.
- [39:32]
A
And that's. Is that different from the people who do the Kera sticks or is that the same company that's.
- [39:39]
B
That used to be do sub, But I don't know. They've all changed ownerships. I'm so untainted in this. Unlike you, Matt. I don't even know who makes it.
- [39:48]
A
Yeah, I don't. So. But Amaloos. Okay, that's useful.
- [39:53]
B
Don't quote me on that.
- [39:54]
A
Okay. All right.
- [39:55]
B
So would like to sponsor this episode. In which case.
- [40:01]
A
So, so Patton, I would take your. Your thing to be that you personally do not like PDT as a therapy. However, you would agree that this had, you know, an 80% ish cure rate and what ABS would be a reasonable 64.
- [40:20]
C
Whatever percent cure rate that was. You have to be histologically clear. And if you were not histologically clear in 40 some or 30 some percent of the cases, that is not 80%.
- [40:32]
B
Was 76% for the gel versus 19% for the.
- [40:37]
C
That wasn't the. The number that I saw in the text was. Here it is. The percentages of participants with complete clinical and histologic clearance were lower. 64.1% of participants in the 10 ALA group showed complete clinical and histologic clearance compared to 4.8%. That's 64.1.
- [40:57]
B
Yes, but that's not 70. What's that?
- [41:01]
C
That's not 76.
- [41:02]
B
No, but, but if, just if you look at histologic clearance alone. So you had to guess, is this clinically clear? So you could have things that were histologically clear even though the investigator wasn't sure it was his. It was like it could be, oh, I think it's still there. And then you take it out. And histologically it's not. So that would be histologically clear, but not clinically clear.
- [41:24]
A
So, Patton, but your, your main thing is you thought, like, they oversold it in the abstract, an article, and they should have not have talked about it so positively.
- [41:33]
C
The ed, the editors should say, like, you can't put clinical and have that be the number in the abstract, like history. We're talking about cancer. Histologic clearance. Put that in there.
- [41:43]
B
It all depends how they wrote the protocol. And what was your primary endpoint? Just saying. All right, Pat, now we know. Now we know what the data are.
- [41:52]
A
So basically we know that this works, right? So if, if, if you. It's a reasonable thing for a patient who was to be like, I don't want to put a cream on for a month and have like an open oozing sore for a month. And I don't want to get a surgery and have a big. I want to minimize my scar while minimizing my downtime. That would be kind of the ideal patient for this.
- [42:16]
B
And I need field therapy anyway for all my AKs, so what the heck, let's try this.
- [42:21]
C
All those other things do. And they're actually better than PDT2. Again, head to head New England Journal of Medicine studies.
- [42:28]
B
Yeah, I agree. If you said, what's a better treatment for AKS? It's 5 fu.
- [42:33]
A
With longer downtime. Right?
- [42:34]
B
With longer downtime.
- [42:35]
A
With longer downtime. I said this would be for somebody who's like, I really don't want to have hamburger face for a month or two months or, you know, 21 days or whatever. Like.
- [42:45]
C
Okay, fine.
- [42:47]
A
All right, Pat, let's go. What do you got?
- [42:50]
C
August 2025 issue, British Journal of Dermatology. Janus kinase signal transducer and activator of the transcript skin transcription signaling pathways involved in the immune mechanism of bullous pemphigoid by Chung et al. So if you've been paying attention, you know DUPY is now FDA approved for the treatment of bp. But if you were really paying attention, you would know that the numbers from the ADEPT trial weren't spectacular. I think DUPY can be a great drug for some of our BP patients. Still a need for non corticosteroid therapy for the patients that don't have that great response. JAK inhibitors appear to be somewhat effective for every other disease in Dermot. So wouldn't they work in BP as well? So, first part of the paper, very basic, sciencey, kind of quickly go through first experiment. What genes are differentially expressed in BP patients compared to controls? Jak3 and stat3 are in there. Interestingly, Jak1 had a lower expression in BP patients compared to controls, so I thought that was weird. Immunohistochemistry Verified JAK3STAT3 protein expression in BP patients compared to healthy controls. Flow cytometry performed on both peripheral blood cells of BP patients and controls. Markers that were measured weren't really different. Blister fluid from BP patients showed high levels of these. I don't even know, CD163 positive monocytes, macrophages. I wasn't really clear what the significance of that population was. They looked at chemokine and cytokine levels in BP patients. Plasma blister fluid compared to plasma of controls and blister fluid of Steven Johnson and 10 and burn patients. You can see the Differences in Figure 3. I'm not going to go into great detail. They did some Eden vitro testing with some of the JAK inhibitors. Tofa, Berry, upa, RITLA determined that TOFA and RITLA had better inhibitory effects compared to oopa. But Berry seemed to do pretty well too, so I don't know. Anyway, they retrospectively evaluated the efficacy of TOFA in a patients with refractory bp. Significant reductions in BP dye and NRS scores, numerical rating, etched scores and all eight patients they seem to reach see complete remission within a few months of starting the tofa. If you look at the BPDI and the NRS scores, significant improvements after starting the tofa. They followed cytokine levels before and after granzyme B, CCl17 CCl, 18 improved and BP180 titers decreased. So I don't think this is a huge surprise that the JAK inhibitors could be something to think about with our BP patients. What do you guys think?
- [45:23]
A
I mean, could be. Could be patent. Looking at the table.
- [45:31]
C
All the patients were put on 8 milligrams of methylprednis alone. But that. That's kind of a low dose. I mean, it's like the numbers. Right? The problem though, with. If you look at like the doopy. If you look at the doopy numbers from studies that were done like this, it's like 76% of patients doopy reach complete remission. And then like when it was really rigorously studied in the randomized, controlled, like it's nowhere near 76%.
- [45:58]
A
Eight out of eight monotherapy, complete remission. Eight out of eight, complete remission.
- [46:05]
C
Yeah.
- [46:05]
A
Right. I mean, that's. And a month after starting the drug, the itch scores went from, you know, sevens, eights and nines to ones and twos.
- [46:16]
C
Yeah.
- [46:16]
A
Like was.
- [46:18]
B
And you wouldn't see that with that steroid dose alone. Right. Would you say that is not what you. The response you get in 100 of people?
- [46:26]
C
I mean, not with 8 milligrams of methyl.
- [46:28]
B
Not with 8 milligrams. Right.
- [46:29]
A
So like 8 milligrams. So methylprednisolone is it 5 to 4.
- [46:35]
C
Right. That's how I think of it. So I think it's 10 milligrams of pred.
- [46:39]
A
Yeah. Isn't it that? I don't know. Let's one of you. I'll look it up. Here, let me. Well, let's one of you look it up while I start. Whenever I go over to doing mine. But I mean, this, to me, this was like. Now I agree with you as well. Not unexpected. Right. But where, where this is going to be like super useful is when TOFA goes generic. Like right now it doesn't. You're never ever going to get, you know, TOPA approved. So really you're limited to Oopa and the other drugs that we have. But it sounds like they thought TOFA would be better, mechanistically so, you know, since it's mostly a JAK3 inhibitor and UPA and ABRO or most, mostly JAK1 2 inhibitors. So maybe this is the disease where so far it hasn't seemed to make a difference. Like a jack is a jack clinically, but maybe this is the situation where it is. But TOFA should hopefully be generic before too long, and this will give Us a great, you know, if the other stuff we've got doesn't work, I don't know. Do you think that 5 of tofa, safety wise, how do you think that's going to compare to rituximab?
- [47:52]
C
I don't know. I, I have used tofa before when, you know, like I had a patient with alopecia areata and before the other ones came out, we did get TOFA approved for them. I mean, I wasn't too. He was young, he was healthy. BP patients are not that.
- [48:09]
A
But I mean, rituximab is very immunosuppressive, right?
- [48:13]
C
No.
- [48:14]
A
Okay. So.
- [48:15]
C
Right. I mean, I've not seen horrible infections in those.
- [48:18]
A
Okay.
- [48:19]
C
Actually do. Okay.
- [48:20]
B
They tolerate era. Right.
- [48:21]
C
Like Covid. There was a bit of an issue in Covid.
- [48:24]
A
All right, but so Pat, if you personally or your relative had to take either TOFA or rituximab, which one would you give them?
- [48:35]
B
Does it depend which relative it does?
- [48:38]
A
Yeah.
- [48:38]
C
No, I think it would depend on severity of disease. So I would say with kind of mild disease where they're not getting away from us, I like, you know, we should bring doopy back into the picture. That's where doopy, I think I'm talking.
- [48:50]
A
Somebody who needs it. Somebody who.
- [48:52]
C
So let's say they fail doopy. If they are blowing up and their titers are really high, I'm going to convince them to go get rituximab. But just because like you blast them with rituximab, B cells go away, titers go down, they come off prednisone. It's, it's really, really nice. If they were in between that mild and blowing up, I think, and I could get them tofa, I think I would talk em into that. Unless they had, I guess, I don't know, thromboembolic stuff. I, I don't know. I don't know.
- [49:23]
A
So you're so basically it sounds like you're saying from a safety perspective you'd probably prefer TOFA over the rituximab a little bit.
- [49:36]
C
I don't know. Rituximab is pretty safe in my hands. I've not seen bad things with it. I would certainly say, okay, patient doesn't want to go get IV tofa over methotrexate, Cellcept and muran cyclophosphamide.
- [49:50]
A
Like, yes.
- [49:53]
B
Anybody. Have you, have you used it in any BP patients yet?
- [49:57]
C
No, the only thing I've used is Ducravacitinib because I had patients with psoriasis and BP and I could get that FDA approved.
- [50:06]
B
Oh, cool. Okay.
- [50:08]
A
Good results if you use much refluomalast yet in bp.
- [50:12]
B
No, it doesn't work for everything, Matt.
- [50:14]
A
That's. I bet it works for bp. Is there any. Is there any evidence, Pat, and I don't know, off the top of your head, do you know, is there any evidence for a premolast in bp?
- [50:24]
C
Off the top of my head, I'm not aware. Okay.
- [50:27]
A
All right. All right. Well, that's a good. It's a good segue into my other. My next three articles. Number one I'm gonna start with here is premolast. And anytime I say a premalast, you should hear that I am saying to use reflum Elast. This was a 12 week open label but randomized trial for Vitiligo. So they did a premolast, so standard therapy plus a premolast versus standard therapy without a premolast. And so it was open label. So hard to know, like, whatever. Now their, their standard therapies were, you know, tailored to the patient. So they had some people who got narrowband, some people who got topical steroids, some people got aryl steroids, somebody got, you know, a lot got topical tacrolimus, but that was all pretty evenly balanced. Biggest takeaway the. The premolast worked. So premolast was better. So the. About 90% of people, their disease was halted compared to 70% of standard therapy alone. But more importantly, repigmentation. About 90% of people, 14 out of 16 had repigmentation going on compared to 2/3 of people getting standard therapy. So basically the takeaway here is that tells me the PD4 inhibition. I don't know how well it works for Vitiligo, but this gives me some evidence that it does something. And so it now gives me yet another disease where I've got an easy, completely safe, extremely cheap drug that I can use as my first line agent for listeners, regular listeners. You know that there was also recent evidence that Plaquenil, 200 milligrams once a day, so very low dose has some efficacy. And vitiligo. So now we've got two non immunosuppressive drugs that we could use as combination therapy if we wanted to invite Eligo, staying very cheap and very safe.
- [52:30]
B
Just confirming nobody got a topical jack in that study. Right.
- [52:33]
A
Ooh, interesting. Let me see here. So the study was out of India. Let me see here. So here's what people got. So a couple people got narrowband, few per, some four or Eight people got systemic steroids, most of them got topical steroids, most of them got topical tacrolimus. One person got azathioprine. And no, nobody got, nobody got a topical jack. All right, so PDE4 inhibitors. Now let's, we're going to stay there and go to another PDE4 inhibitor or another PDE4 inhibitor article. So this time we're going to go to psoriasis, which is again, regular listeners will know I stay away from psoriasis. This was a study that was funded by the makers of a premolast title of it. Oh, and I didn't give the title of my last article, sorry. So if anybody wants to look it up, it was a premolast add on benefits over conventional drugs in unstable non segmental vitiligo. A 12 week single center ran randomized controlled trial. This study is benefits of earlier a premolast initiation in patients with psoriasis and limited skin involvement. Results from a real world retrospective study. Here was the takeaway. People with a little bit of psoriasis, so mean BSA in this study was roughly 5%. The people who got a topical and never went on from a topical did not do as well as people who got a premolast. And early apremolast initiators got, you know, dramatically better a lot faster than a lot earlier than late eprelast initiators. And so then whenever you look at the data, if you had a little more bsa, you were more likely to get early a premolast. If you had less than 5%, you were less likely to get a premolast early. The main takeaway was even for people with mild psoriasis, it makes a lot of sense to put them on a PDE4 inhibitor. Even if they've got just a few percent BSA, you're much more likely to get them to clear or almost clear if you initiate premolast early, which again in my mind means you initiate reflum elast early even in people with mild psoriasis.
- [54:53]
B
Okay. I will also say it's harder to have a significant PASI response in people with more mild disease. So if you're like, oh, the people who you know, and maybe they got it later, right. So if you got somebody with a PASI of 4 and somebody with a PASI of 8, it's easier to get a PASI 75 response in the PASI of 8 than in the PASI of 4. And the PASI of 8 is more likely to get drug early than the PASI of 4.
- [55:16]
A
Yes. And they. They did. They actually did a good job here. They, and I should have said this, they used BSA as their main outcome measure in order to kind of account for that. So it was getting people down to, you know, less than 1% BSA or 75% improvement in BSA. And it just happened much sooner if you started premolast sooner, so. And then. Patton, anything you want to add there?
- [55:47]
C
Nope.
- [55:48]
A
Not another plug for reflumelast.
- [55:51]
C
No, we love reflumelast. Yes, we do.
- [55:53]
A
We do.
- [55:54]
C
Vitiligo, psoriasis, everything now. Yeah, everything.
- [55:58]
A
And then my last one is another psoriasis AD1. This was just the first good article I've seen about. So this was Characteristics and management of follicular events and contact dermatitis in patients using Tapinrof cream for the treatment of atopic dermatitis. So this was a kind of a deep dive into the follicular events in their clinical trials. Main takeaway, most common on the legs, it had an earlier onset in atopic dermatitis than it did in psoriasis. So in ad, the typical onset was about two to three weeks. In psoriasis, it was at about a month. So then the things that seem to make it more likely are perspiration, occlusion, or overuse. So using it like twice daily, and then there's no specific therapy recommendation. Basically, you know, it was stop the drug to the affected areas. If it goes away, assuming it goes away, which it will, typically within a week or two, you can start the drug back up. You know, if. If you want, you can try some topical steroids. You could try a carotlytic, especially in psoriasis, you could try, you know, OTC Adapalene, but basically it is temporarily discontinued. The Tapiniroff I. E. Vitama. Assuming that it goes back, that it goes away, then you can restart. Once it goes away, that's pretty much it. Now, if the disease went away, obviously you don't need to discontinue it or to restart it. But assuming the disease is still there once the follicular events are gone, you restart it. So nothing new here really, other than most common on the legs. And it happened earlier in AD Than it did in psoriasis. Those were kind of the. The two takeaways. Patton, I'm guessing you hate. I think I guessing you don't like Fatama or do you love Tama is great. Okay. Patton loves Fatama. Ferris, what are you. I know you like Vatama. Anything. Any pearls from either of you with Vatama. For either psoriasis or ad.
- [58:18]
B
Yeah, I just. I think you just have to tell people here are the side effects that can occur. And like, if you got the folliculitis, don't be freaked out by it because patients do not like it when they get it. I don't know. I. I had some of the earliest cases in the trials. I tried like topical clindamycin lotion. Didn't really.
- [58:35]
A
Yeah.
- [58:35]
B
Maybe wasn't the most effective thing, but, you know, we didn't. Maybe I would try a little topical steroid and just say, wait it out now.
- [58:42]
A
Yep. And the. For anybody who's not familiar with it, it does. It looks more like Keratosis pilaris than it does a like inflammatory KP than it does regular old folliculitis. The pearl that I usually use is that especially for people who've had psoriasis for a while and have used topical steroids before, I will always give. Tell them to use Clobatazole once a day and Vitama once a day for the first couple of weeks. Because otherwise I've had people come back and be like, I use this for like two weeks. I didn't see much. Clobazole works much faster, so I just stopped it and used my Clobazole instead. So I usually will do the two together for the first two weeks and then tell them once you're, you know, once it's a lot better. Stop the Cliptazole, use just the Vitama. Because we're trying to get the remitter effect where then you won't have to use anything for a long time. That's. That's my psoriasis fatama pearl. All right, that I think, does it for this week's episode. Any last comments from either of you?
- [59:41]
B
No, it's hard to compete with six papers.
- [59:44]
A
Oh, Ferris, just because I said that you usually do things that are too erudite. Erudite. I don't even see that that's how you know if you're erudite or not is if you.
- [60:00]
B
That's right. If you can pronounce it.
- [60:02]
A
If you can pronounce it. All right, so thank you. I want to say thank you to all of our listeners for tuning in. I hope you learned a few things. I hope you laughed once or twice. And mostly I'm hoping you're planning to join us next week. Until then, I'm Matt Zyrus.
- [60:19]
C
I'm Tim Patton.
- [60:21]
B
And I'm Laura Faris. And we are Derms on drug.
- [60:25]
A
Sa.