A (3:09)

I almost started recommending spirulina because there was a study that showed it might have some benefit. A probiotic that had lacto case of bacillus rhamnosus and spirulina had some efficacy for acne. Forget that. I'm gonna get rid of their acne and give them dermato.

B (3:28)

Yeah, don't do that. Maybe you can have them go in the sun right after they take their spirulina too to really clear it up. But no. So spirulina 61% of the patients, that's what they took. The other, the other one was elderberry, about a quarter and then Ashwanda, 11%. And then there were a few other ones that were, that were in there. So, you know, the thing that was interesting here was what they were looking at was myositis, myositis specific antibodies and myositis associated antibodies. And they compared the herbal intake to the non herbal intake group, and there were significantly lower rates of antibody positivity in the group that had herbal intake associated dermatomyositis. So, you know, this is why I thought it was important. So if this looks like, man, that looks like dermatomyositis. The biopsies suggestive, but they've got negative antibodies. You know, don't make sure that you're getting a good supplement.

B (4:32)

You know, history in these patients. So they may have negative antibodies, but they've got the disease.

A (4:38)

So here's what, when I read this, I thought, hey, it's good to not have any antibodies. The antibodies probably make your myositis worse or they're markers, you got cancer or whatever. So the, the, the, the herbs are helping. They're getting rid of your antibodies.

B (4:54)

No, I don't think it's getting rid of your antibodies. I think you know, antibodies, these antibodies are probably in very many ways markers. They're not necessarily the pathogenic antibody. And so, you know, it just, I don't think that it's a good thing. And you know, one of the things that they would, that I had asked her when she presented this at Pitt was, you know, what if they stop their spirulina? And it turns out that some people still do have persistent disease. So I think people do get better. Ask it, what's up?

A (5:24)

But some people do get better.

B (5:26)

I mean with, with anything. Some people can get better. They don't have a good pa. They don't have a good study that I saw on like treatment resistance. Right. So, you know, but I think it's important to ask about this. I think it is important certainly to have them stop it. There is some, you know, there are some like mechanistic, mechanistically plausible ways that this could happen. So spirulina can increase tolike receptor 4 activation in vitro in patients with dermatomyositis cells when it's treated in vitro with spirulina. The other one that actually has come up to, not necessarily in this one, but is isoline, which is this like weight loss alfalfa based, like natural weight loss product. And that has been associated with increased levels of tumor necrosis factor interferon alpha and interferon beta. So know, why do we need to know this? You know, one, this doesn't make people's med list so you have to actually ask about it. Two, if it looks like dermatomyositis but it's not perfect and you don't see, you know, any of the auto antibodies. Think about the, you know, herbal supplements and you know, and then, you know, counsel patients like, who are maybe like autoimmune diathesis type patients to avoid these, you know, these drugs. Now one of the, you know, confounding factors that they acknowledged in this paper is that we know that things like viral infection can also trigger, you know, flares of most autoimmune diseases or you know, autoimmune on onset of new autoimmune activity, you know, might patients have had a viral infection and thought, I'm going to take this spirulina echinacea to get better. And was it that, was it the herb or was it the infection that they were like self treating with the herb. So there could be, you know, that could be a confounding factor. But I think it's important to know especially spirulina and you know, when you've got like young kids or, you know, children who like to get smoothies with all kinds of herbal things. I'm like, avoid spirulina.

A (7:31)

Okay.

C (7:32)

All right.

A (7:32)

I like it. Spirulina. Got to ask about stuff that's cheap, that's easy. And I'm a big fan of cheap and easy. Okay. All right. Dr. Patrick, Dr. Patton, what do you got?

C (7:45)

My first six pack paper is titled From Inflammation to Circulation Biologics Reduce Clot Risk and Hidradenitis Supper Tiva by Alam et al in the November 2025 edition of the International Journal of Dermatology. I guess there was a 2024 JAD publication highlighting increased risk of venous thromboembolism in HS patients. I can't say I specifically remember, but sure. Increased inflammation and HS and that leads to clots. I can buy it. So these authors wanted to see if biologic therapy for HS had any effect on clotting, so they went to Trinetics. Are we. Are. Do we like trinetics? Are we anti trinetics? Are we still undecided?

A (8:28)

I'm becoming slowly anti trinetics. I think it's just when I, like I said, I tried to do like a little bit of a study in it and it was just so the way they report the data that HS1 you did where it was like, no, every. Not everybody who's taking this drug is like, I couldn't. I can't figure it out. I can't figure it out.

C (8:46)

Yeah, yeah.

B (8:47)

Too complex for map.

A (8:48)

If I can't figure it out, then it's not figure out.

B (8:51)

Nobody.

C (8:51)

It's not. It's not legitimate fairs. Where are you with trinetics?

B (8:55)

No, I, I am. We just got it at unc. So I'm actually like, when I get some free time, I want to learn it a little bit better. Even better. Find a med student who will learn it a little bit better. And I want to play around with it.

C (9:07)

All right.

B (9:08)

And see, so I'm excited for it. Okay.

C (9:10)

All right.

A (9:11)

Well, with it, Ferris, we're. You're going to tell us if it's baloney and obviously it's not baloney. It's real data. But just is the way the data sifted, like can you make.

C (9:20)

How much do we trust it? Do we say, hey, yeah, there may be something there or I'm just going to ignore this. Like fares, right? Fares were done with we completely spontaneous.

B (9:30)

Vaccine reporting side effects.

C (9:33)

Like, we're like, yeah, okay, so trinetics hasn't reached that point. Yet, so still hope. All right. There were over 15,000 HS patients who received biologic therapy. This included etanercept, adalimumab, infliximab, secukinumab, ustekinumab, and even Anakinra, which I thought that was interesting. BIMI was not on the list, I guess because it was newer. These were matched with 1500. No, 15,000 HS patients who had not received biologic therapy. And the odds ratio for both venous thromboembolism and pulmonary embolism were low in the biologics group. Odds ratio of 0.56 for VTE and 0.61 for PE.

A (10:16)

But it.

C (10:16)

And that's in the. The table. I forget which table it is, but we'll have it on there. But the HS patients on biologics were just kind of like, healthier overall. They had lower odds ratios for diabetes and chronic kidney disease and elevated cholesterol. They had an odds ratio of 0.4 for tobacco use. It seems that the propensity score matching, like, should have included that. They just kind of did, like age, race.

C (10:43)

Gender, maybe, things like that.

C (10:47)

Maybe that would be harder to do. I don't know. I've never done trinetics, so.

B (10:52)

Yeah, yeah. The less you match on, the more, like, matches you can get, but the less similar they'll be. Right. And so then you can do, like, logistic regression to try to adjust for all these different factors. But it's like, then you're getting into complicated statistics. So.

C (11:11)

Yeah, I mean, you know, I think HS patients often want to go on biologics. It's not like you have to sell them on it. I, I will continue to prescribe it. I don't know that I'm going to be strongly suggesting that, hey, there's all these added benefits. You won't get blood clots if you go on biologics. There was this paper, and one of the biggest reasons why. And we looked at this with metformin, right. HS patients on metformin, I also think was trinetics. And it was like, decreased risk of cardiovascular. I mean, it was like these really impressive numbers. But the problem is.

C (11:44)

When you have patients on these therapies, let's say they've gone through every single biologic that there is and they're not any better. I can't see myself saying, well, look, you need to stay on it because of this decreased risk of clots that I read about in this one paper. So I, I don't know. I, I don't know what to make of the paper. I don't think it's, you know, like I said, you try biologics, patients want to oftentimes go on them. I don't know that I'm going to be trying to sell patients on there's other benefits aside from disease control.

A (12:15)

That's actually a super interesting question to me. If the clinical efficacy of a biologic, say we're talking about psoriasis, where we know that biologics reduce cardiovascular morbidity mortality or they seem to.

B (12:31)

I don't know that we know that.

A (12:32)

But, but we think yes, we think so does the efficacy predict that it's an impact on risk of this other stuff. So if it. Right. So if it doesn't get your HS better, it would be intuitive to me that it's not really going to help that much with your cardiovascular risk because it's not really reducing your inflammatory burden. Right. Kind of a deal like that. The other thing that was interest fascinating to me looking at this was I still think that there is a huge component of no matter how well you try and match it, somebody who is capable of getting on a biologic is different from somebody who's not capable of getting on a biologic. Like that is a marker for a level of health, consumer sophistication. Right. Being able to get on a biologic and that a lot of they do.

C (13:25)

They, they mentioned that confound. You know, those patients are coming into your office, you're monitoring them much closer. They're seeing just doctor. They're getting doctor care more than the patient's not on the bio. So all of that's going to benefit patients. It's not just the biologics.

A (13:41)

Yes. And even beyond the care that they're getting as part of the biologic and the hs, they're just better healthcare consumers. Like they're answering their phone, they understand how their insurance works. They, you know, whatever. They're just different. So even if you match them based on interaction with the healthcare system, you'd still be like, well, the people who get on biologic. Or it's, it's a marker. It's a marker.

C (14:03)

Yeah.

A (14:03)

You know. Okay, so good stuff. Let's jump over to, to my first two. So I, I am too.

A (14:13)

Add. No, I'm not ADD Ish. I'm, I'm, I'm too superficial to go in depth into one thing. So instead I'm going to go shallow into two. All right, so my two.

A (14:23)

Articles here for this first part. Number one, the efficacy of combined oral isotretinoin and desloratadine or levocitirizine versus isotretinoin monotherapy in treating acne vulgaris. A systematic review and meta analysis. Randomized controlled trials. So I've been talking about this for at least 10 years. We're now up to in this, they found 10 studies, 675 people in randomized trials. Generally, it was relatively lower dose isotretinoin than we usually use. More like 20 milligrams a day or 0.25 migs per kig, which is again, about 20 milligrams per day, although some of the studies use normal dose isotretinoin. But the main takeaway here, this is super cheap and easy. So first, all that's been studied is des, loratadine and levocitirazine. But loratadine gets metabolized to desloratadine. So you should be able to use loratadine, which is as close to free as you could possibly free and totally safe as you could possibly get. And by adding DES, by adding it to isotretinoin, they had eight fewer inflammatory lesions at 12 weeks compared to people getting the same dose of isotretinoin. And they had a 50% reduction in the probability of getting cheilitis. And so it was a thing to me. Like, it's so cheap and easy. We probably ought to be like, hey, and by the way, get some generic loratadine and start taking 10 milligrams of Loratadine a day together. With the isotretinoin, does it actually do anything or not that's clinically meaningful? Don't know. But it's completely safe and extremely cheap. Is kind of my, you know, I.

B (16:03)

Read these studies and, like, I know that's out there. I'm always like, yep, I gotta do this. It's like just the habit, right? Like, it's so terrible, the habits that we have that make us not do this. Like, a couple times I've done it when somebody's complained about the tolerability or why is it not working? Why am I not responding? You know, you sometimes have those people, you're like, I've actually been on six months of a mig per kig of isotretinoin. Like, I feel like you're not budging. So, like, I'll pull it out when I need something to get them through this, the colitis, or to get them, you know, a little better efficacy. But we should just start, like, putting it in our regular counseling, write the script or whatever, put it in your dot phrase. And epic, if you're an EPIC user, like, we just gotta, we should just do it. It's like, it's silly.

A (16:50)

There are two things we should be doing. Everybody with that. We started ISO tretinoin should be going on high omega 3 fish oil. Good data that that reduces cheilitis and nosebleeds. And loratadine, the fish oil is harder to take. They're bigger pills, they're more expensive. But the loratadine is just so cheap and so easy, even if it makes a little bit of a difference. But yeah, it's, it's, you know.

A (17:14)

Remembering to do it right. And, and you're trying to get through. You're trying to get them enrolled in I pledge. You're trying to do. Talk about this, talk about that and the blah, blah, blah. It's like one of those things that, like, how much stuff can you throw into the visit, you know, is a big part of the way you think about it. Yeah. All right. My second thing there was a quick hitter to stay kind of in the acneiform distribution of things. Someone's called TICT T Y K E D off by Rosacea. An Australian case series of rosacea associated with Dukeravacitinib. Basically was just a case series of seven people who had pretty classic papulopustular rosacea show up once they went on Ducravacitinib. When I looked at these patients, it actually looked to me even more like Demodex than it did like typical papulopustion. We just talked about an article a few weeks ago from the inflammatory bowel disease literature where JAK inhibitors caused, like, lots of people to get Demodex infestations. So although questionable if a tick, you know, is a tick inhibitor, same thing as a JAK inhibitor, who knows? But just an interesting thing to have in the back of your mind if, if you have a patient, you start on a Tick two inhibitor and they get something that looks like rosacea. It could be from the tick 2 inhibitor and these patients had to come off of the drug. They were bad enough that. And we got enough other options, that kind of stuff. But Ferris, is this something that you, you know, follicular disorders, are they like a real thing with, with TIC2s and psoriasis?

B (18:51)

Yeah, I, I think you can see some of the Jack, like, like Jack knee type stuff with tick 2 inhibitors. I have seen that before. Tim, have you seen that?

C (19:02)

I don't have too many people on tick twos and. But the people I have, that's not been an issue.

B (19:07)

Yeah, I mean, I wouldn't Say it's like common. But I, you know what I think is like, did they, they didn't look for Demodex in these patients.

A (19:16)

I did not see that they did Demodex. I don't think they did like Demodex preps in them.

B (19:20)

So it would be interesting. Like, I've seen patients, you know what I mean? Like, I've seen patients and like one case, like a guy who's on a course of prednisone and just got like fluoride Demodex. Right. And like we see that happen sometimes. And I mean, that's an easy thing to treat.

C (19:36)

Yeah, they, they mentioned in the paper that if you decrease IL13, that's actually decreased bad in terms of, you know, demodex population. Apparently IL13 helps us keep Demodex growth in control. But I'm not really aware of Demodex being an issue with, you know, any of the drugs that we use.

A (19:57)

That, that Block Isle in 2017, that was my leading theory for the Demodex for doopie conjunctivitis. And then when doopie red face came out was, you know, Demodex is a parasite. IL13 is involved in. It's in, it's in the label. We should be worried about parasite infections. These drugs are letting parasites run wild. But treating as. And there actually were a couple of publications hypothesizing this, but it hasn't played out as like that the IL13 actually, IL13 inhibitors actually.

A (20:32)

Seem to impact Demodex at all.

B (20:34)

I can remember one of my DUPY patients in Pittsburgh having horrible Demodex after I started. Like, she had bad add, never had rosacea, came in horrible rosacea. It was all like, flora Demodex. So. And I was like, oh, this makes sense. I feel like I've had that. I've seen that a couple times, so it would fit.

A (20:55)

When the red face stuff started to come out, people really thought about it then as well. But I think it does happen. It's. But the red face is usually more malassezia driven than it is Demodex. Whenever we, whenever we see the red face with Doopie.

B (21:11)

Yeah, but I do think the pearl is like, particularly if somebody's on a new immunomodulatory or on an immunomodulatory drug, if all of a sudden they've got papulopustularization, just look for Demodex and you know, if you can treat that. And like I did with this person, she was great. Treated her through it. The DUPY was life saving for her. Bad ad. Look for it because you might be able to treat through it.

A (21:32)

What's your. What's your Demodex? Go to Ferris.

B (21:36)

So I like oral ivermectin. You know, do it. I do it once a week for four weeks. I also do like the. The triple rosacea triple cream with ivermectin, metronidazole and azelaic acid.

A (21:48)

I do. I weekly Ivermectin combined with oral metronidazole. There was a study like 15 years ago looking at this, and it was more effective, substantially more effective than either one by itself. I think ivermectin usually works. But when you put ivermectin and metronidazole to get. So it's ivermectin, you know, every week. And then the metronidazole, this, what was studied was 250mg tid. You start it the same time you take your first dose of the ivermectin. You do that for two weeks and then you're done and you transition them over to the triple cream. The other thing with Demodex is you want to put the topicals on at night before they go to bed. Because the Demodex come out of their pores and walk around on the surface of their skin at night while they're asleep.

B (22:32)

Is this a theory or is this proven?

A (22:36)

I think of that as true.

B (22:38)

You think of that as true. That does not mean it is.

A (22:40)

All right, I'm gonna look it up while you're.

B (22:42)

I've got one more pearl for Demodex for you that I learned accidentally top if you'd like, when people. You cannot clear it. 5 floor uracil. Give them Effudex.

A (22:55)

Oh, right. It's toxic. I learned this.

B (22:58)

I had a. An old surgeon who is in Pittsburgh, who was in Pittsburgh, who I'd given him, you know, topical affidx. And he come, you know, like three months later, comes up into my office, like, I'd like to see Dr. Ferris. And he was the kind of person who could do that. And he's like, this is my secretary and she had this bad rash. I gave her my cream. She's better. You need to investigate it. So I go through her chart. She had rosacea and Demodex. He gave her affidavit. And of course it's like a, you know, intercalating agent. It basically, it's like if I bathed all of us in five floor years, so we would die.

C (23:37)

Yeah.

B (23:38)

So it's chemo. It's chemotherapy, but I actually have tried it a couple times when I've had people at recalcitrant Demodex, and it's helped. So I'll label you.

A (23:48)

That's. You've said a lot of smart stuff over the years. That's my favorite thing ever. 5 fu for demodex right there.

B (23:56)

Oh, that's right.

A (23:57)

Okay.

B (23:58)

That's right. All right, all right, you heard it here.

A (24:00)

All right, all right, all right, let's. Let's move on to our next article. Farris, what do you got?

B (24:05)

This is me. Okay. I'm back with one of my favorite drugs because it was back in the New England Journal of Medicine or one that I'm most excited about. This is oral Icotra kinra for plaque psoriasis in adults and adolescents. So this was New England Journal, Robert Bisson et al New England Journal of Medicine, iconic lead, phase three studies. So Iotra kinra. This is a targeted oral peptide that you take daily that blocks the IL23 receptor. So 684 participants, adults. They had to be adults or adolescents 12 or older. So about 10% of the people in the study were adolescents. The rest were adults. Randomized 2 to 1. Icotra can have 200 milligrams once a day or placebo. People were excluded if they had failed or had an adverse event with aisle 23 targeting biologic. In the past, they were. They took the single tablet with water. They had to take it after waking and no food for 30 minutes after. But one interesting thing was that for, if they had, for adolescents who couldn't swallow tablets, they could actually just dissolve it into water and drink it. So I thought that was kind of interesting just because it's like, you know, kids don't like needles, kids can't swallow pills. What do you do with them? So that, that was kind of interesting. So who were these patients? You know, BMI on average was 29 Pazi scores of 19 to 20, which are high but not as high as we used to see. They also did look at scalp disease. So, you know, the percentage of patients who had scalp disease was. Was pretty high.

B (25:50)

And it was. And their IGAs were, you know, predominantly three, some fours. And so. Okay, so CO primary endpoints, Pasi 90 IGA 0 or 1 at 16 weeks. So what did they see at week? 16 IGA 01 clear, almost clear. And 65% treated with Icotra Kinra versus 8% with placebo Pazi 90 and 50% versus 4% with placebo Pazi 100 rates. You know, the thing that we really love to see, 27% of treated patients versus less than 1% now. This was at week 16. And, you know, IGA zeros were kind of similar.

B (26:37)

You know, if we look over time, because they did the study actually went out to 24 weeks. Yeah.

A (26:42)

So when I was looking through this, which shockingly, I looked at it ahead of time, are we now. Are they now commonly reporting IGA01s as an outcome measure in psoriasis? We where like, is that now considered on par with Passy?

B (27:00)

Like, yes, yes, the FDA likes IGA01.

A (27:05)

And do, you know, off. So in AD, I'm very comfortable saying what IGA01 means. IGA0, obviously, you don't have anything. IGA of 1 in AD means barely perceptible to a trained observer. We are trained observers. So it's barely perceptible to us, not perceptible to the patient. So somebody who's got an IgA of one, the patient says, I'm totally better. And we say, ah, you're not quite. Totally. Tiny bit of this there. How do you clinically think of IgA1 in. In psoriasis?

B (27:38)

So it should be static and it should be that erythema is, you know, barely perceptible, minimal elevation and minimal scale. I mean, IGAs and psoriasis, we don't like because they don't take into account body surface area. So, you know, to me, it's like, they're like, wow, look at that. You're so much better. Do you have any psoriasis? And it's like, you know, there is a little bit here and here and here. I'm like, okay, that's an IGA one, right. As long as those are not significant appearing plaques. If you really had very, very thin, light red plaques over 90% of your body, I'd have a. I'd be hard pressed to call you Iga1, even though if you're a sponsor of a study I'm on, I know that it doesn't involve the body surface area.

A (28:24)

So.

A (28:26)

I looked it up while you were whatever. And there is a report. So you're. You were very prescient. In 2014, in the journal Cornea, they reported that 5fu was highly effective against demodex blepharitis.

B (28:43)

Wow.

A (28:44)

So you.

B (28:44)

Okay. Don't use it on the eyes, though. I'm not recommending that.

A (28:48)

I know it was eye drops and they was a.

B (28:50)

Okay.

A (28:51)

But it was. The main takeaway was. So five FU did kill the debodex. So good. Ferris, I'm impressed.

B (28:58)

Thank you.

A (28:58)

Okay.

B (28:59)

Thank you. All right, so. Yeah, so that's that. I thought you were going to be impressed by my IGA scoring. Okay. Other, like, key things. Adolescents, again, there weren't tons of them. Pazi 90 rate was 70% versus 14 on placebo. So I thought that was good. And then, you know, safety stuff was mild uris. Okay. Key things that I thought were really interesting here. 48 patients had latent TB infection at baseline. And of those, 20 of them did not get. Did not get treated for it. So you could go into the study with latent TB, not get treated, and none of them developed TB activation. Now, I get it's only 24 weeks, but I think like, this may be a drug that we don't actually have to do TB TB testing for. So I thought that was like one of the more interesting things. So there was an accompanying editorial. Their, you know, thing was, you know, yes, that's great. Like 2 to 3% of the population has psoriasis. They don't like it. You know, what are we going to do about the fact that, you know, like, this is going to be. It's going to be incredibly expensive. So from 97 to 2025, spending for psoriasis drugs in the US increased by more than 2000% in constant dollars. That's not adjusted. And the average wholesale price for the first year of therapy for Most biologics exceeds $100,000. That is again, micromedics red book. That's not, you know, that's not including all the, you know, the, whatever rebates and everything, but interesting study. Interesting to me, the, the latent TB not being treated. I've never been able to do that in a psoriasis study, so.

A (30:50)

All right, Farris, we've talked about icotra Kinra a number of times now here on derms, on drugs, and I know that you still. Nobody knows the actual answer to this, but where do you think it's gonna fall efficacy wise compared to. Does this give you any new information on where you think this drug's gonna fall efficacy wise comparatively to our existing therapies?

B (31:15)

Yeah, I mean, it's going to be better than a premolar to crav a sitinib. It's probably going to be around the stellar ish efficacy. It's going to be better than, you know, it's going to. I'm going to put it between like Stellara, not quite tremphy.

A (31:29)

Okay, all right. Fair and oral and hopefully no labs and the Whole thing. Do you have to know, is there a PDUFA date yet? Do we have an idea?

B (31:38)

I do not know. That does not mean that there's not one.

A (31:42)

And in this study, it was once daily or twice daily.

B (31:45)

This was once daily.

A (31:47)

All right. And you do have to take it. Not with food or something.

B (31:50)

Yeah, so it's like, don't, you know, take it. It's fall with water. Don't eat for 30 minutes. So, you know, again, it's an absorption thing. It's not like.

A (32:00)

Yeah, you know, man, it's not going to hurt you. It just.

B (32:03)

It's not a safety thing. It's an absorption.

A (32:05)

Yeah, it's an absorption thing. So you take it first thing in the morning before you. Yeah, okay.

B (32:09)

All right.

A (32:10)

Okay.

C (32:12)

There's similar data with TB in the biologics, isn't there? I mean, not that it was part of a trial, but definitely in trials, but. Yes, but definitely reports of latent. And when we say latent tb, we're saying A positive. Their quant gold was positive. Their chest X ray was negative.

B (32:30)

Yes.

C (32:31)

Okay. Right. So, I mean, you know, I think that. I don't know that I coach or Kinra is like, safer than the biologic that block aisle 23. No, because there's pretty fair data.

B (32:45)

It's. What are you going to get in your label from the fda, Right.

C (32:48)

Yeah, right, right.

B (32:49)

Dermatologists do not like to check blood work. And you would. You would not have a leg to stand on to put somebody on Tremphy or Skyrizi without a quantifer on gold. If.

B (33:03)

Insurance won't do it. If they developed it, you wouldn't. I mean, it's in the label. You would not. If they develop tb, A, insurance won't let you do it, and B, if they develop tb, you would. You would find somebody who would testify against you. This is in the right. If it's not in the label and insurance cannot require it, and you can actually give patients a drug without having to check any blood work. That's going to make a lot of things really easier. A lot easier. I still say that is the whole reason why, you know, that has been the behind much of the success of a Tesla, so.

C (33:36)

Oh, absolutely.

A (33:37)

Yeah, Abs. Absolutely. All right, Patton, what do you got?

C (33:43)

My second six pack was titled A Premalas for Oral Mucosal Predominant Resistant Pemphigus Vulgaris, a Promising Adjunctive Treatment by Zang et al in the November 20122025 edition of oral Diseases. Most of the authors are from Wuhan Hospital, which I think I would just say I'm from somewhere in China. If people ask, I'd be like, it's.

B (34:05)

Like the Harvard people, like where are you from? Boston.

C (34:08)

Yeah, right. I'd be like.

C (34:11)

Somewhere in China, like the middle of it. You've never heard of it although one of the authors was from UNC.

B (34:18)

Oh, Dr. Jilou in my department, yes.

A (34:22)

Cool.

C (34:22)

So Dr. Zhang, the lead author, had published some other stuff about pemphigus and a premolast didn't appear to be effective for moderate to severe PV. Could be used as monotherapy for PF. There was a patient with IgA pemphigus that had apparently a decent response. So definitely some sort of mixed evidence in the literature, but it kind of suggests certain phenotypes may respond better. I've definitely had pemphigus patients that present with oral mucosal disease exclusively or oral mucosal disease and skin. And after corticosteroids and rituximab like skin lesions get a lot better. Oral disease also improves, but they continue to have these like nagging erosions and gingival sloughing. It's like they're better, but it's not like it go. The oral disease goes into a complete remission. And that's kind of tough because what do you do in that instance? Like they're way better. It's not life threatening at this point. Do you go aggressive? Do you keep giving you more rituximab? Add ivig? I don't know what to do with these patients. They can be tricky. So this was a prospective non randomized study. Five patients, they had oral predominant pv, some of them had skin, but it was pretty limited. And they continued to have active oral mucosal disease despite 12 weeks of prednisone plus minus mycophenolate. Rituximab is like kind of standard of care. But none of the patients like they weren't called recalcitrant but yet they hadn't received rituximab. So I thought that was a little bit odd. Anyway, each patient was then treated with a premolast standard dosing that we do, building up to 30mg twice a day eventually. And prednisolone 0.5mgs per kg. Figure 2 had a bunch of line graphs detailing improvements in the pemphigus disease severity index. Desmogline 3 and 1 titers. Prednisolone dose was able to be decreased in all the patients. It's probably worth a try. I mean when patients are combined with systemic corticosteroids, it's always hard to figure out. And if you're not significantly decreasing desmogline 3 antibodies, like the change in the antibody titers, just really weren't that impressive. There was like maybe one patient where Desma glean one was this huge difference. But the DesmoGline 3, it's kind of like maybe a little bit less. And this guy stayed about the same. And so if you can't decrease antibodies, how effective is a medication going to be for pemphigus? We, we always kind of learn that, you know, if the antibody's there, it doesn't have to activate complement, it just binds to desmogline3. And that's sort of what triggers the disease. If you're not getting rid of the antibodies, can you really effectively manage pemphigus? There was a few sentences in the discussion about how a premolast may strengthen the cytoskeleton, counteracting the effects of antibody binding.

C (37:15)

It's, I mean, right. A premolast. And we would probably use Roflumilast because they. I wish that we did have a Flumel last sponsor. It's just not going to happen, is it because it's generic? Yeah. Oh, well. But, you know, these are tricky patients, like I said, and a Roflum elast is easy to give, tolerated relatively well. I don't think it's unreasonable to try. I just wouldn't be surprised if, like, the response wasn't fantastic because they did give the patients prednisolone at the same time. And that's always, always hard to tease out, you know, what the non prednisolone treatments are actually doing.

A (37:54)

And there is definitely data that, yeah, the PDE4 is inhibition is good for your cytoskeleton. So I could certainly at least buy that it's working by sort of.

A (38:11)

Protecting the cells a little bit from the effects of the antibodies rather than getting rid of the antibodies. Yeah, like that's viable. I see it. Okay. Do you think you'll be using Reflum elastic early in pemphigus at all? Is there any chance of that or is it.

C (38:33)

No, really. Where I see this is just in the, this, this case. You know, I was talking, I think Donna Colton was on our show earlier and, you know, she was talking about what do we do with these patients? They don't really have high titers, but they continue to have oral disease. I talked to her. She. She had actually been starting like, intralesional rituximab just in the mouth, maybe try and get some resident B cells out of the way. And maybe that's what's causing disease. I mean, so. So no, I. I wouldn't start this initially, but for those. Those patients where they just have this persistent, you know, every time they brush their teeth, they're bleeding, or if they eat a certain food, it's like, ah, I really hurt when I ate this particular food. And, you know, oral, like oral erosions and ulcers, that's just miserable, right? APIs ulcer.

C (39:24)

Makes your life miserable for the one or two weeks that it's there. Just like, imagine that being, like, constant. It's. It's a lot of morbidity, even though, you know, you saved their life because they came in covered in blisters. Rituximab, prednisone. They're way better, but they're really miserable. So I'm gonna try it.

A (39:42)

Okay. All right, fair. All right, let's jump onto my last two. So first one.

A (39:49)

Fascinating to me. So, reversal of partial botulinum toxin, a resistance following Janus kinase inhibition with tofacitinib, a series case series. So this was two cases of people who had, you know, been getting various toxins, and the toxins were working less and less. By the time it got to the point of these case series, it was only working for three weeks. And then they gave them tofacitinib for a couple of weeks and gave them an inject, you know, more toxin, and it lasted for three months. So the problem with this, right, obviously from the first, the idea of, like, are we gonna give somebody a potentially toxic drug so that their Botox will last longer?

A (40:39)

It mechanistically truly doesn't make any sense. Because if the toxin is just being neutralized by an antibody, if you put them on a JAK inhibitor for three to six months, sure, I could see your antibody titers going down, but this just. It shouldn't work. It shouldn't have any impact on the antibodies within a couple of weeks. But it was just interesting and something that I was like, ooh, I wanna talk about that on the podcast. Can we improve our cosmetic injection outcomes by giving people jack and now those drugs? There'll really be a reason to have them if they can help make Botox last longer. Right?

C (41:23)

Finally, good use.

B (41:25)

Just not be resistant to it, Right? It didn't really make. It wasn't like, oh, it's not making it last longer.

A (41:32)

Well, made it last longer in these patients in whom it was only lasting three weeks. But in, you're right. In normal people, it wasn't like it made it go from three months to six months or six months to nine months or something. Yes, I, I would agree. So that.

B (41:47)

Yeah, this was all done in Beirut, Lebanon. I mean, like, you know, I'm trying to imagine trying to do this here. And like they put people on methotrexate. If one person was put on methotrexate.

A (41:59)

Yep. To see if they could get their Botox to work better. Right. Yeah. So that's trying to get that through.

B (42:04)

Insurance will be next.

C (42:06)

I thought the, I thought the woman that got methotrexate had alopecia areata and that's why they were giving her methotrexate and that's why she actually got the jack too.

A (42:14)

Yes, that, that actually was true, I think.

B (42:16)

Okay, Okay. I just saw the methotrexate and I was like, this is kind of crazy stuff.

C (42:21)

Yeah, that doesn't make a whole. Yeah, yes.

A (42:23)

But just, you know, letting our listeners know it's out there now in case a patient comes. It's the kind of thing now that I could see a patient looking up like, Botox doesn't work in me anymore. What can I do? And they come in, you know, wanting to be on Zell Jams.

A (42:36)

So now the other one was just something that I think derms, we need to just be very aware of. I don't think it's anything we're actually gonna do, but it was just interesting. So scalp cooling therapy in chemotherapy induced alopecia, addressing variability in cooling duration and efficacy. So the basic idea here, and this has been around for quite a long time, that if you put like a cooling cap on somebody's head before the, the chemo starts and then while the chemo's being infused and then for a little while after they get the chemo, you can really reduce the severity of the chemo induced alopecia. The assumption of course is at least mine, is that you're restricting blood supply to the scalp. And so as a result you're not getting as much chemo that's going to be toxic to the, to the rapidly proliferating hair cells. And this really was just back to the old idea that it's a reasonable assumption most of the time to say that more is better, but it's actually not the case here. So first, two different main types of chemo used in breast cancer. So there's taxanes and anthracyclines. This is. Cooling is highly effective with taxane. So like 90% of.

A (44:00)

Women in breast cancer. So. And these are used in cancers other than breast cancer, too. But the studies are all in breast cancer.

A (44:07)

Basically, 100% of people who get a taxi will lose all their hair when they get treated for breast cancer. But if you do the cooling, about 90% of them will protect the majority of their hair. But the, you know, in some of these protocols, they're doing it for, like, four hours after your infusion. You're supposed to sit there with the cold thing on your head. Really, the data is 30 minutes before the infusion. Then 30 to 45 minutes after the infusion seems to be just as good as doing it longer. And then the other one, anthracyclines, it's much less effective. So again, about 100% of people will get severe alopecia with an anthracycline, these cooling things. So 90 minutes of post infusion, again, you do probably 30 minutes before. And then 90 minutes of post infusion reduces, like, severe total alopecia down to 50%. And if by 50%, and if we do it for 150 minutes, two and a half hours instead of an hour and a half, it reduces total alopecia by 70%. However, the frequency of needing to cover the scalp with something was still 70%. So. Meaning it prevented people from going, like, completely bald, but made their hair thin enough that they still were wearing a wig or wearing a scarf or a hat or something like that. So the anthracyclines, the takeaway is it doesn't work as well for those, but still is worthwhile. And it's an interesting thing. And something that I've actually talked to a few friends who got breast cancer was like, oh, make sure you talk to your oncologist about, you know, doing the scalp cooling so that you don't lose your hair. And it really did make a very big difference for them in their quality of life. So it's just definitely worth us as derms knowing that this is out there. And I thought it was just interesting that it wasn't necessarily the case that more was better take away.

B (46:08)

I think these are actually covered by insurance now for women undergoing chemotherapy for breast cancer, I think in some places it's covered.

C (46:18)

So do the cancer centers typically provide these devices, or is it something that the patients have to kind of get on their own?

A (46:25)

No, I think it's a device that they literally have in the infusion center because you're. You're there in the. It has to be. It's not like you don't have to do it, like every day. It's.

C (46:36)

So do they offer it to everyone, like, or is it. I'm just surprised that a person would be like, yeah, I don't want that. Isn't everyone getting this then?

A (46:46)

It's a good question. So let me. I'm going to AI that right now. Does every breast cancer patient.

A (46:54)

Get offered scalp cooling and is it covered by insurance?

A (47:02)

I can literally feel the AI making me dumber as we speak.

B (47:06)

Yeah.

B (47:09)

Yeah, no, I think that. Well, I don't know the coverage, but I think it's good for patients to know, to ask about it. And it's good to have actually, like, you know, data to say, you know, how long to do it. I think people actually have to get them. Have to get them, like, as their own device.

B (47:30)

I don't think that it is like, here, here's your IV and here's your cooling cap. Like, I think people have to actually have to have them.

A (47:38)

So let's see, let's see.

B (47:40)

And they need a prescription and all that, I believe.

A (47:43)

Okay, so interesting. Let me see if AI agrees with Ferris or not. Here, let's see here. Do patients get their own device or does the center have it? Come on, AI, I was going to ask you that.

B (47:57)

How many times in your life do you, have you guide been guided by the theory that, you know, if less is good, more is better all the time. Yeah. I feel like this is like one of your guiding principles.

B (48:11)

Explains a lot.

C (48:13)

Anyone who knows you well, it explains a whole hell of a lot.

A (48:16)

It does. So most patients use a device provided by the infusion center, but some systems require patients to rent or purchase their own cold caps and bring them to treatment.

C (48:27)

Yeah, I mean, it's probably site specific. It looks like the one at upmc. I mean, they have a whole page here.

B (48:37)

They probably mark it up.

C (48:39)

We offer cooling. Yeah, we offer cooling therapy to people receiving chemo.

A (48:44)

Okay. Okay. Interesting.

B (48:46)

All right.

A (48:47)

All right. Well, I. I want to thank our listeners for joining us this week. I hope you learned a few things. We hope you laughed once or twice. And mostly we're hoping you're planning to join us next week. Till then, I'm Matt Zyrus.

C (49:00)

I'm Tim Patton.

B (49:01)

And I'm Laura Ferris. And we are Derms on drug.