Why you shouldn't ever use Bactrim for acne (and other new info you don't want to miss)

Summary

Derms on Drugs – Episode Summary

Episode Title: Why you shouldn't ever use Bactrim for acne (and other new info you don't want to miss)
Date: January 30, 2026
Hosts: Dr. Matt Zirwas, Dr. Laura Ferris, Dr. Tim Patton

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Overview

This episode of Derms on Drugs features the panel's signature "six-pack" format, where Drs. Zirwas, Ferris, and Patton dive into six timely studies and hot topics from recent dermatology literature. The episode is packed with practical clinical pearls, lively debate, and sharp (occasionally self-deprecating) humor. The headline warning: vital new safety data makes Bactrim a dangerous—and potentially medico-legally risky—choice for acne management.

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Key Discussion Points & Insights

1. Mediterranean Diet for Psoriasis (01:05–12:36)

• Study: JAMA Dermatology – Mediterranean diet in patients with psoriasis (Mediso RCT)
• Study Design: 16-week, open-label, evaluator-blinded RCT; 38 patients with mild-moderate psoriasis.
• Intervention: Full Mediterranean diet (dietitian support, monthly counseling, free olive oil).
• Findings:
  • Significant PASI reductions (3.4 mean decrease vs. 0 in controls).
  • 68% reached PASI 50, 47% PASI 75, 26% PASI 90 in Mediterranean group.
  • No significant weight loss or lipid changes, but improved DLQI and sleep.
  • Quote – Dr. Ferris:
    "They did not lose any weight, they just ate better and their psoriasis improved." (05:24)
• Practical Implication:
  • Mediterranean diet improves psoriasis independent of weight loss.
  • Diet likely works via microbiome modulation.
• Memorable Moment – On Olive Oil:
  "They also got.. free extra virgin olive oil. And they had to eat at least four tablespoons a day." (02:52)

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2. Modifying Immunosuppression after cSCC in Transplant Patients (12:39–21:36)

• Study: Transplantation Direct – Consensus on immunosuppression after cutaneous SCC in kidney transplant patients.
• Key Points:
  • For 1 low-risk SCC, nephrologists seldom recommend immunosuppression (IS) changes.
  • For multiple/high-risk SCCs, consider switching mycophenolate or a calcineurin inhibitor to an mTOR inhibitor.
  • Panelists favor keeping CNI (e.g., tacrolimus) due to graft protection.
  • Dermatologists should match IS discussions to level of skin cancer risk.
• Clinical Debate:
  • Dr. Ferris suggests considering nicotinamide for lower-risk fields; both hosts note field therapy and oral preventives.
• Quote – Dr. Patton:
  "I think everyone kind of agrees...lots and lots of AKs...not the person where you need to call up the transplant team and say, hey, we should switch something." (16:46)

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3. Atopic Dermatitis and Contact Sensitization Meta-Analysis (21:36–30:36)

• Study: Systematic review/meta-analysis on AD and risk of contact sensitization.
• Key Outcome:
  • No significant difference—patients with AD are neither more nor less likely than non-AD to have positive patch tests to contact allergens.
• Notable Findings:
  • AD patients slightly more likely to sensitize to sesquiterpene lactones (marigolds, chrysanthemums).
  • Diagnostic confusion may inflate apparent contact allergy rates in AD.
• Quote – Dr. Zirwas:
  "Main takeaway was we're now can be pretty sure that people with AD...they're no more or less likely to be allergic to anything compared to everybody else." (23:18)
• Humor:
  • "Get your AD friends chocolates, not flowers. That's the takeaway." (23:22, Dr. Ferris)

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4. Dupilumab for Haley-Haley Disease – Promising Observational Data (30:36–27:26 [out of sequence])

• Study: Multicenter cohort; 20 patients; dupilumab in ATP2C1/“Haley-Haley” disease.
• Results:
  • 70% of cases: dramatic improvement, 20% improved, 10% no response.
  • Strong evidence for effectiveness; mechanism not entirely clear.
• Alternative Therapies Discussed:
  • Oral magnesium (300mg/day), apremilast, topical diclofenac, glycopyrrolate.
• Quote – Dr. Zirwas:
  "14 got, like, dramatically better. Like, so 70% got, like, shockingly better." (24:27)
• Naming Tangent:
  • Disease to be renamed ATP2C1-associated non-syndromic epidermal differentiation disorder.
  • "Yeah, because that rolls off the tongue." (27:44, Dr. Ferris)

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5. Cosibelimab (PD-L1 Inhibitor) for Advanced cSCC (32:06–39:39)

• Study: Pivotal open-label—cosibelimab in metastatic/locally-advanced cSCC.
• Mechanism:
  • PD-L1 inhibitor with direct tumor lytic action.
• Results:
  • Objective response ~50%; complete response ~13-25%.
  • Durable responses; lower grade 3+ immune AEs than PD1 inhibitors.
• Quote – Dr. Ferris:
  "Kind of the take home, about half of people are going to respond and if they do, that's probably going to be a pretty durable response..." (35:10)
• Discussion Point:
  • PD-L1 status poorly correlated with response.
  • Highlights emerging role of this new, less toxic class.
• Memorable Moment:
  • "If I had a squam and they were talking to me about therapies, I would do the PD-L1. Like, it just makes way more sense." (37:58, Dr. Patton)

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6. New Dermatomyositis Malignancy Prediction Tool (39:42–44:44)

• Study: JAMA Derm—TIP CA model for cancer risk in dermatomyositis.
• TIP CA Factors:
  • T: TIF1γ antibody
  • I: [no] Interstitial lung disease
  • P: Poikiloderma
  • C: Clinical diagnosis (DM vs. cutaneous only)
  • A: Anemia
• Implementation:
  • Points-based; cutoff at 2.5 separates lower vs. higher risk.
  • Similar to ICAMS model but with added poikiloderma, anemia.
  • Sensitivity (82%), specificity (66%).
• Quote – Dr. Patton:
  "If you have dermatomyositis and you don't want cancer, then you'd rather have interstitial lung disease." (42:21)
• Debate:
  • Original scoring inconsistencies; practical use vs. ICAMS tool.

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7. Bactrim Warning – The Medico-Legal Bombshell (45:14–49:33)

• Key Point:
  • Recent FDA warning: Bactrim (TMP-SMX) in young, healthy patients for >7 days confers a 1 in 3,000 risk of fatal acute respiratory failure.
  • Most commonly prescribed for acne; the risk applies even in the absence of comorbidity.
• Discussion:
  • Risk much higher than SJS/TEN.
  • Need for extreme caution, particularly with long-duration Rx.
  • Co-hosts agree: Bactrim should be last-line; other options are safer.
• Quote – Dr. Zirwas:
  "If you're a derm and you prescribe Bactrim twice a week...over a 30 year career, that's going to be 3,000 people. You will kill one person from this reaction." (49:16)
• Reactions:
  • Dr. Ferris: "I hate Bactrim as a drug for acne and I'm always happy to have a reason not to give it." (47:45)
  • Dr. Patton: Comparison to other sulfas, but most data specific to Bactrim.

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Notable Quotes & Segments by Timestamp

• [05:28] Dr. Ferris:
  "They did not lose any weight, they just ate better and their psoriasis improved."
• [23:22] Dr. Ferris:
  "Get your AD friends chocolates, not flowers. That's the takeaway."
• [24:27] Dr. Zirwas:
  "14 got, like, dramatically better. Like, so 70% got, like, shockingly better."
• [35:10] Dr. Ferris:
  "About half of people are going to respond and if they do, that's probably going to be a pretty durable response..."
• [37:58] Dr. Patton:
  "If I had a squam and they were talking to me about their therapies, I would do the PD-L1. Like, it just makes way more sense."
• [42:21] Dr. Patton:
  "If you have dermatomyositis and you don't want cancer, then you'd rather have interstitial lung disease."
• [49:16] Dr. Zirwas:
  "If you're a derm and you prescribe Bactrim twice a week...over a 30 year career, that's going to be 3,000 people. You will kill one person from this reaction."

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Conclusion

• Key Takeaway:
  • Never use Bactrim for acne due to its unacceptable and under-recognized risk of fatal lung injury in young patients: "You will kill one person over your career if you use Bactrim liberally."
• Other Highlights:
  • Advise the Mediterranean diet for mild-to-moderate psoriasis.
  • Be familiar with evolving tools for immunosuppression management and malignancy risk in dermatomyositis.
  • Monitor new oncologic approvals, especially drugs with better safety profiles (cosibelimab).
  • Continue to scrutinize clinical literature with skepticism and humor.

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Transcript

[A]

Welcome to season two of Derms on Drugs, a video podcast brought to you by Scholars in Medicine, the best educational platform of dermatology and provided no cost to medical providers. Derms are drugs is where cutting edge dermis hit or miss comedy. I'm Matt Ziers from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Fares from the University of North Carolina, Dr. Tim Patton from the University of Pittsburgh. And we use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of derm and have some fun listening. New episodes drop every Friday on Scholars of Medicine, Apple Podcasts, Spotify, the other major podcast platforms. The video component has the key figures and tables from the articles that we talk about. This week we've got another one of our fantastic six pack episodes where we are going to get into the latest, greatest, coolest stuff in the literature. And I've got to throw a plug. You better listen to the end because there is a new thing out there that is a huge medico legal risk for dermatologists. But let's go ahead and get started. Dr. Farris, what do you got?

[B]

Okay, my first paper today is from JAMA Dermatology. It is called Mediterranean diet in patients with psoriasis. The Mediso randomized clinical trial from Perez Butello et al. These are a bunch of Spaniards who did this study.

[A]

So Mediterranean authors for a Mediterranean diet.

[B]

Exactly. The diet is as Mediterranean as the authors. That's the way it is. All right. Javier Perez Butello. And I'm sure I'm saying that right. It's probably Butillo or something. Anyway, okay, so patients always say, hey, what can I do to change my diet? Or some patients actually ask like, would a Mediterranean gluten free, whatever diet help? So, you know, normally we're like, we don't really have a lot of data for that, but now we actually have some. Okay, so this was a study that was an open label, single center evaluator blinded randomized clinical trial done in Madrid. So patients had to have mild to moderate psoriasis, like a Pazy of 2 to 10. They had to be on stable topical therapy only. And then they were randomized one to one to either get a Mediterranean diet intervention or just a standard, you know the advice like, hey, eat a good healthy low fat diet but no real other intervention. Okay, so this was small. 45 patients screened, 38 patients randomized, so 19 per arm, 97% of them completed 16 weeks of follow up. So that was pretty good. And everyone kept using their, like topical steroid calcifetriene regimen. Nobody could start on a systemic therapy. So the Mediterranean group, they got like the full on Spanish grandma kind of treatment. It was. They had a dietitian guiding them, they gave them counseling, they gave them educational material. They called them once a month for 20 minutes, which is probably more than my grandma even did for me. And they also got. This is the best part of it. I would have gone into it just for this. Free extra virgin olive oil. And they had to eat at least four tablespoons a day.

[C]

Okay then, yeah, at this point, biologics are cheaper.

[B]

No, this is not true. Is cheap and so is extra virgin olive oil.

[C]

Okay.

[B]

All right. Controls got a one time low fat diet handout. And no, like, they didn't have the dietitian supporting them. So obviously you could not blind the patient to this, but you could blind the evaluator and primary endpoint change in PAZI score. And then they also looked at stuff like, did you actually adhere to the Mediterranean diet? Dlqi, sleep, I don't know, why? Anxiety and depression with the hand, with the heads. And then they also did look at things like bmi, some, you know, some, like metabolic parameters. Okay, so what actually happened? So baseline groups, the medium Pasi was like 4 to 5, BSA was 4%. So these were definitely more mild. They were pretty well matched to weight, cardio, cardiometabolic profiles. So they had some anxiety. They did have higher elevated CRPs.

[A]

All right, all right, get to it. Did the diet work?

[B]

It worked. Pazi improvement. The estimated mean change in PASI was a decrease in 3.4 in the Mediterranean group versus 0 in the control group.

[A]

And where, where did their Pazzi.

[B]

Could you let me talk. This is not the map of Zyrus podcast. All right, so in the Mediterranean arm, 68% had a PASI 50, 47% had a PASI 75 and 26% had a PASI 90 and 11% had a PASI 100. In the control arm, 11% hit PASI 50 and nobody hit 75, 90, 100. So that's pretty good.

[C]

Wow.

[B]

They also looked at like diet adherence. So you could say, well, some people in the control arm, maybe they started following the Mediterranean diet. So there's a way to measure this. And it went up by 8.2 points in the intervention group, but only by 1.3 in the control, and that was statistically significant. So it wasn't just that the control people started eating better. Now we what is psycho kickers? So you're probably like, well yeah, I mean we know that obesity is associated. They just lost some weight because they ate right on. Right. There was no meaningful between group difference in body weight or waist circumference.

[A]

So they did not lose any weight, they just ate better and their psoriasis improved.

[B]

Yes, they ate a health, they ate a better profile of food and then you know, 16, I guess you can lose weight in 16 weeks. But yeah, they had better improve. They had better improvements in dlqi, insomnia, anxiety and they trended toward less depression, but it wasn't statistically significant. Now their lipids did not improve. Their hemoglobin A1C did on the Mediterranean diet. So I thought that was interesting. There was really like no cytokine difference. So they did this high dimensional cytokine panel, like kind of not a huge difference. Fibroglass, Fibroblast Growth factor 23 was a little bit higher. It decreased a little bit higher. Actually decreased more in the control group. It really explain anything. So and then also 63% in the Mediterranean diet group de intensified their topicals versus 17% of controls. So you know, I kind of some good data that if you eat, you know, the Mediterranean diet, which is like olive oil, fruits, grains, lower meat, that, you know, that is something that we can tell people to do.

[A]

So this is, I mean these results are impressive and it's hard to like, I can't remember in my whole career somebody ever coming in and being like, yeah, but rises is a lot better because I'm eating better.

[B]

Like I have had that happen a couple times, like where patients have said I've really gone to like a high vegetable diet and I have done better. And it wasn't really significant weight loss that it was associated with it. I also like, I. We can go down this rabbit hole at some point later, but I really think diet probably matters for some of these diseases like hs. You know why, why do some areas and some pockets get horrible HS and other areas that have a lot of obese people don't. You know, not everybody with obese, with, with HS is obese. I really firmly believe that there has got to be something. Environmental diet seems to be the most obvious candidate.

[C]

Yeah, I had a patient with really, really horrible scalp psoriasis and we were at the point where we were discussing biologics and when she came back in for a visit, her scalp was completely clear. And that's what she said. She goes, oh, I, I changed my diet and I was kind of like, huh? And like, I didn't go into details of what she exactly did. But, I mean, it's impressive.

[A]

It's. It's very viable from a microbiome perspective.

[B]

Right.

[A]

Because a Mediterranean diet's also good for your microbiome and like, for example, an ad. And it should matter in psoriasis as well. When you've got a healthy microbiome, you produce these indole metabolites that activate the aryl hydrocarbon receptor. Right. The exact same thing that Fatama does. So a good diet, maybe it's like Vitama. Systemically, whatever is one of the effects, like microbiome route?

[B]

Yeah, there's a lot of this. So, like, fascinatingly, in the melanoma world, there's a lot of evidence for microbiome impacting response to immunotherapy from fecal microbiotal transplants actually making people go from being PD1 resistant or, you know, progressing on PD1 inhibitors to then becoming PD1 responders to. There is data that patients who are prescribed and given a high fiber diet actually have better responses to PD1 inhibitor than patients who are not. There's evidence that having antibiotics prior to starting immunotherapy decreases your response to immunotherapy. So like there, there is real stuff. I used to kind of think it was all a little like crystals and, you know, chakras. But I actually think there's something real.

[C]

To it is, did they say how hard or easy it was to. To like, how hard is it to just switch your diet over to Mediterranean diet?

[B]

You know, people did do it, so they didn't do a lot of like, how hard was it? But I, you know, I think it's probably what people with resources and knowledge would tend to do. Right. People with resources and knowledge tend to be good at saying, I'm not going to eat as much, you know, processed food. I'm going to make sure I eat more healthy, you know, vegetables and grains and, you know, cook with olive oil and not, you know, butter and all those things too.

[C]

So I think I'm just moving to Greece or Spain or something. There's the answer.

[B]

You could. We'll find a time to record our podcast while you're there.

[A]

Having been to Greece, Spain and Italy, main thing I think is those people. It is just so sweet. They do. It is so laid back and chill. None of these people hustle at all. Was my. Has been my main takeaway from Italy, Greece, Spain and Portugal.

[B]

Yeah. And the food is Different. Right. Like they are eating like real. Like when I go to those places, I feel, I don't feel disgusting versus like going to like a all inclusive resort or something. Right. Like you eat, you know, grilled fish, you eat vegetables, you know, you don't have massive quantities. There's not like grocery stores full of, you know, prepared processed food. I mean, I, it, it does make sense.

[A]

I saw some interesting stuff about gluten sensitivity this week. That. Gluten. Gluten sensitivity. And for people who are just listening, I'm using air quotes. Gluten sensitivity spiked in 2006. 2006 was also whenever they fig out that glyphosates in particular Roundup, if you apply them to wheat right before you harvest the wheat, it desiccates the wheat so dries it out and it stores much better and much longer. And so there's some now belief that all of these people with non celiac gluten, you know, gluten sensitivity, it's actually more because wheat has a whole bunch of glyphosates in it now. And that also explains why some of these people will say, well, I can eat European when I go to Europe, I, I'm not gluten sensitive anymore because in Europe their wheat is not treated this way. If any of that's true or not, I have no idea. But it was just interesting.

[B]

My dad worked for Monsanto growing up, so Monsanto funded my childhood. So we're gonna be like nothing bad was rounded.

[A]

No Monsanto. Great company, Great company. But it is an interesting also AI use that. I think it's gotten much easier because you, you really can't. If, you know, if you go in and ask chat, GPT or any of them about the Mediterranean diet, like, could I eat this, should I eat that? You actually can get good answers.

[B]

Really say, make me a week long Mediterranean diet, you know, dinner plan. I like these things. I don't like these things. And you could get it with recipes. Yeah. So no, I, I think it's, it's good data. Eat the Mediterranean diet. Fish, meat, veg, lean meats, vegetables, whole grains, olive oil.

[A]

Yep.

[B]

All right.

[A]

Peasy, Patton, what do you got?

[C]

All right. My first six pack was December 2025 issue of Transplant no Transplantation Direct and is titled consensus based recommendations on the management of immunosuppression after squamous cell carcinoma diagnosis in Kidney Transplant Rec International Deli, Consensus statement by Whitley et al. So as we all know, transplant patients are at a higher risk of developing cutaneous sec they get more of them. And the ones they get are bad dudes. They're. They're really challenging cases. They can be. There was a Delphi panel of derms that was published in 2021 in Jamaderm. Address this a little bit. One of the things come out of that article was the actinic damage in skin cancer index. The ad went from one to six. One being patients with photo damage, but no AKs, six being risk. The development of a high risk cutaneous squamous cell carcinoma based on a 2021 study. Discussion with the transplant team regarding immunosuppression should be initiated for stages five and six. So stage five is invasive. Multiple invasive squamous cell carcinomas. They grouped it into five A and B. You know, lots of, you know, not many versus lots of them. And then stage six, which was a high risk cutaneous squamous cell carcinomas. But for stage 4 patients, first invasive low risk cutaneous SEC. No consensus was reached. So this Delphi panel, the one that I'm talking about now, that was the JAMA one. This one had a few dermatologists on it, but most of the participants were kidney people. They called themselves international transplant nephrology experts, but I'm calling them kidney people. There were three rounds. They focused on ADSCI stages four, five, and six. So again, four, that's your first invasive squam. Five, multiple low risk invasive squames. And six is a high risk invasive.

[A]

Squam is high risk. Like, oh, you got one on your ear. So now that's. It's a high risk, or is it like high risk based on tumor characteristics?

[C]

There was.

[B]

It's.

[C]

So they. The Brigham and Women's Risk thing. So it's 2B and higher was high risk. And I think with 2B, you have two or more risk factors. Risk factors being like perineural invasion size greater than 2 cm. Help me out here.

[B]

Tumor.

[C]

Yeah. Poorly differentiated. Yeah, stuff like that.

[A]

Truly high risk tumors.

[B]

Not like, oh, yeah, oh, it's on your scalp. Yeah.

[A]

Yeah.

[C]

Okay.

[A]

All right, got it.

[C]

So they asked the respondents if changes in immunosuppression would be made and what would these changes be. The complete surveys and the supplementary materials. It was kind of long, a lot of questions. 31 panelists completed all three rounds, and the results are nicely summarized in Figures 1 and 2. So for Stage 4, Adsei, that's actinic damage skin cancer index. Is that what I called it?

[A]

Yeah, that's it.

[C]

Actinic damage and skin cancer Index, you had one low risk scc, they wouldn't consider changing immunosuppression. So they kind of like the stage four where there was not that consensus with the derms, with the kidney people. They're like, now we wouldn't. One low risk. We're not going to really bring up that conversation. Multiple low risks and high risk sec. There was consensus to modify immunosuppression, immunosuppression if the patient was on azathioprine, which I don't really see that much, so I don't know how relevant that is. And there was near consensus, so close to like 70% that with multiple SCCs, consider modifying the metabolite, if it's mycophenolate, mofatil, and then switching either this, the calcineurin inhibitor or the antimetabolite to an MTOR inhibitor. If patients are having a high rate of secs or high risk scc. Other factors that they took into consideration probably more detailed than what a derm is going to do. You know, history of T cell or antibody mediated rejection. It was kind of straightforward. And so I think for us as derms, you have your transplant patient, you know, lots and lots of AKs. I think everyone kind of agrees. That's not the person where you need to call up the transplant team and say, hey, we should switch something. They get one sec, maybe bring up that conversation. And certainly with multiple and high risk, then you, you bring it up. The percentages of physicians that change immunosuppression after a few low risk sccs was higher than. Than like my personal experience, a fair number of times transplant docs are happy with the fact that a transplant is not being rejected. And if a patient has some low risk secs, like if you think about a few on the trunk, they're, they're, you know, well differentiated. There's no perineural invasion. I have not had them be really that open. They're just kind of like, I would just kind of keep everything the same. So the percentage in this particular paper was higher than what my personal experience was, but other than that, it was pretty straightforward. Did you gu. You guys have any other takeaways?

[A]

So this is probably not a question you can answer, but why isn't everybody who gets a kidney transplant just on rapamycin? Like, if, if squutaneous squams are such a big deal and rapamycin is so protective, why don't they all just go on it right from day one? Is there a big downside? I Don't know about.

[C]

They, it does have a worse side effect profile. I couldn't get into details, but they don't like the side effect profile and they don't think it works as well in preventing rejection. Right. I mean when you say to them like, hey, let's switch off of this tacrolimus over to sirolimus, they're like, like if it's a heart, they're like we, we need to save the heart and switching over to sirolimus, that would concern us more. That's been my experience. I couldn't give you numbers but you know, that's why one of the ones was, you know, maybe taking my away and adding the MTOR inhibitor as opposed to stopping the cni. That's why they kind of set it up in this trial as they have an option. You could stay on a cni, but maybe instead of the mycophenolate, that's where you add in an MTOR because they, they like the CNIs. They, they like tacrolimus.

[B]

It's good at preventing rejection. Yeah. And what would be interesting would have been to combine this with like the derm guidance. Like me, you know, looking at this, if you were in that group that was like the, the couple one to two lower squams, like maybe that's where based on some of the data we should think about nicotinamide. Right. And then like I would also like guidance on where do we talk about field therapy? Like should, like, you know, should we be doing field therapy? Once somebody has any AKs, we're like, if you have AKs, you got to do field therapy at least once a year.

[C]

You know what? That JAMA derm consensus addressed that. Hold on, I have that like right here. I pulled that up for a second. Consensus based recommendations. And they use that same actinic damage and skin cancer index. And so what they said this was the 2021 Jamaderm Stage 1 Photo Damage Stage, skin only preventive measures, education, sun protection, sunscreen, blah. Discrete AKs. So you had scattered AKs, cryotherapy, oral chemo preventive therapy should not be initiated. Group dayks, same thing. Field, that's when you have field therapy. Oral chemo preventive should not be initiated. But if they have thick lesions then you do field therapy. Fluorocil based modality, blah, blah blah. Field cancerization, field therapy, transplant team don't discuss immunosuppression. You're right, they didn't get into nicotinamide. The, the kidney people, they actually did talk about that. Field treatment or nicotinamide with like your stage 2, 3 diffuse actinic damage things.

[B]

Okay, so they don't have an objection to that. They're like. Yep, yep, sounds good. Okay.

[C]

No, yeah, they, they, they liked that recommendation.

[B]

I like it. Thank you.

[A]

And would we guess now that we know that the reason that vitamin D, cuspatriene and fluuracil work so good together is this long lasting immune response. I don't think there's any reason not to use them together. But my guess would be that you wouldn't get as much benefit in transplant patients compared to 5fu alone because it's seems like the immunosuppression is going to make it less likely you're going to get the immune surveillance you're hoping to get.

[B]

I think we just don't know.

[A]

Yeah.

[B]

Until we do the study.

[A]

Yeah, we do. Got to do the study. Ferris, get UNC Derm on it. Ferris.

[B]

All right.

[A]

All right, let's jump on to mine. So first one was association just came out literally today. Association between atopic dermatitis and contact sensitization. And updated systemic review and meta analysis. So this is a long running question of are people with AD more likely to have contact derm than other people because their barrier is impaired and they use more products or are they less likely to get ACD compared to other people because their immune system is skewed 2h2th2 and contact sensitization is more or less a TH1 takeaway from this article was they it was a big review with like dozens and dozens of studies included in it and there's no big difference. So if you look at people with AD who get patch tested compared to people without ad, you get patch tested, no big difference. The only things that were of interest, people with AD were more likely to be allergic to sesquiterpene lactones. So things like chrysanthemums and marigolds and some weeds, they don't have a good explanation for that. The best one that I've got is that aquaphor has sesquiterpene lactones in it. So it's got an ingredient in it, one of the aquaphores, that's the common background one. It's got an ingredient called Bisabolo, which is an extract of German chamomile. But they also said it could be airborne, whatever. But the main takeaway was we're now can be pretty sure that people with AD, they're no more or less likely to be allergic to anything compared to everybody Else. That was kind of the big. The big takeaway.

[B]

Flowers. Get your ad friends chocolates, not flowers. That's the takeaway.

[A]

That's good. Get them chocolate, not flour. I like it. Ferris. All right, let's. My second one, which is a little bit more sort of clinically relevant here. Efficacy and safety of dupilumab and Haley Haley Disease multicenter cohort study. And to be honest, it was impressive. So this. Obviously, it's not a randomized controlled trial. Right. But this was. They had 20 patients with Haley Haley. 14 got, like, dramatically better. Like, so 70% got, like, shockingly better. Four improved, but it wasn't shocking. And there were only two who didn't get any better. They didn't get any worse, but they also didn't get any better. It was pretty darn impressive. And it's really interesting. You know, we now have data for dupilumab in both Haley Haley and Derrias. And I have no idea why it works. Like, none. Like, it certainly seems like it does.

[C]

But I. I read a thing on aisle four, and IL13 bind to, like, something called spork. And that can affect intracellular calcium. And so if you block IL4 and IL13, they're not acting on that thing. And calcium, intracellular calcium homeostasis somehow gets fixed. That was the bat because. Right. We think of Haley Haley as a. I mean, you could have secondary inflammation. I get. But the primary problem is, like, just cellular adhesion. Adhesion. Right. Yes. That's not an inflammatory process as far as I would think of it.

[B]

No. And those pictures are, like, dramatic.

[A]

Yeah, yeah.

[B]

It's crazy. I. I have seen. I tried this, like, off label once with somebody with Haley Haley, and she definitely did get better. It'd be great to have. I mean, having stuff like this is really helpful in terms of advocating on behalf of our patients to get coverage for these drugs.

[A]

As I was digging into this, a few other things that if you. If you can't get the doobie covered and you don't have samples, none of this stuff do, I think works great. But it's stuff that's outside the door and that has some data and literature to back it up. Oral magnesium. And so it's 300 milligrams a day of elemental magnesium. Could be magnesium chloride, magnesium chloride, hexahydrate, magnesium glycinate, whatever. But 300 milligrams of elemental magnesium. And that makes some sense because we know that magnesium is calcimimetic, somewhat mimics calcium's effects in cells. So Since Haley Haley and Dairy A's are a problem with calcium transportation, makes some sense that magnesium could play a role. Can't hurt. And it is dirt.

[C]

Dirt cheap.

[A]

The two other things.

[B]

Magnesium glycanate is a good adjunct for insomnia.

[A]

That's right.

[C]

Calm.

[A]

Calm Mag. Calm is one of the things that I see advertised all the time. And then the other things that have some data out there. So a premolast. So oral reflumelast. Worth a shot in these people if you've got a difficult patient. And then topical diclofenac. So mostly 3% is reported. But topical 1% diclofenac, which is generic over the counter and super cheap, also reported. Could help with the pain, but also did seem to help with healing the lesions. And then glycopyrrolate either orally or topically also had some benefit in Haley Haley. So. But the big thing here, doopy 20 patients look really strong and just useful to have in your back pocket if you see a tough Haley Haley patient.

[B]

Paper that we should talk about at some point is now we've renamed. There's been this whole effort to rename everything. It's no longer called Haley Haley disease. Now you want to call this ATP 2C1 associated non syndromic epidermal differentiation disorder. Yeah, because that rolls off the tongue.

[C]

I'm just gonna call it Haley. The one Haley was a great guy. The other Haley was a big jerk. Yeah.

[A]

Okay, can we call it the nine familiar pemphigus.

[C]

Yeah.

[A]

Bfp. Isn't that what they used to call it?

[C]

Yeah, yeah. Benign familiar. That protein was smok1s, M, O, C1 smock1. Anyone keeping track?

[B]

I heard it here first.

[C]

Hey, I want to say that that atopic derm study, I think are. Aren't you. You're selecting for patients that went and got patch tested. And I would argue that, yes, genetic atopic derm, lifelong history, blah, blah, blah. Okay, fine, that's one group of people. But the other people that you're sending to get a lot of patch testing done are these late onset atopic derm that don't have the lifelong atopic diathesis. So aren't you comparing atopic derm with atopic derm?

[A]

So. So yes, what I think is happening with a lot of patients is they have derm and they don't. They don't know if it's derm, ad contact derm or whatever. And so I think there's a lot of diagnostic. Like this person has a diagnosis of ad. This person doesn't it is a difficult situation. And there's some. They did kind of break it up into pre2016 and post 2016. Because back pre2016 more likely, like if you got called AD, you had like classic AD. Post 2016 it was more likely to be you're called AD or you don't really have any. And they saw not that big of a difference in pre2016 there was actually negative correlation. AD patients were less likely to have contact derm, but it was a very small effect and post 2016. So from 2017 on they showed no effect. But I agree completely. The whole sort of space of non obvious dermatitis, it's hard to make heads or tails of any of the literature. Right. Because the only time you know somebody has contact derm is once they get better, whenever they avoid something.

[B]

Right.

[A]

Because you can have atopic dermatitis or just dermatitis. We don't know why. And a positive patch test that seems relevant doesn't mean the passive patch test is relevant. You know, it's almost like saying that everybody with joint pain and a positive ANA has lupus. No, you can have joint pain and a 1 to 80 speckled A and you probably don't have lupus. So I agree. Takeaway, take away. I agree.

[C]

It's.

[A]

It's hard to figure out. All right, let's go to our next one. Ferris, what do you got?

[B]

Okay, moving on to big things like cancer, but still, squamous cell carcinoma. Efficacy and safety of cosabellumab in advanced cutaneous squamous cell carcinoma results from a pivotal open label study with a median follow up of greater than or equal to two years. Emily Ruiz. And so, so what is Cosabella mab? It actually sounds very Mediterranean to me. That's my theme of the day. If you had to come up with that. Its brand name is unlocks it, which is kind of a cool name too. Okay, so Cosabella Mab is not. It inhibits the PD1 pathway, but it is a PD L1 inhibitor. So what does that mean? It is. It binds to PD L1, which is the PD, which is the ligand BUR versus or it is the. The ligand versus receptor. So it blocks the PD. If it blocks the. Let me start that over. Cosabellumab binds to PD L1. It blocks its interaction with PD1 and B71. So this is still the like taking the brakes off the T cell activation and the tumor microenvironment side. But you're talking about blocking or binding onto the tumor side instead of the, the receptor side. The other twist is that the FC domain of this antibody, cosivelumab, has been engineered such that it can induce antibody dependent cellular cytotoxicity or complement dependent cytosofticity. So you actually have direct tumor lytic activity.

[A]

So in like real cancer, where they're doing, and I know squams are real cancer, but like in lung cancer or whatever, wherever, they're using PD1 inhibitors all the time. Does this stuff work? Work better? Does the PD PD1L work better than PD1?

[B]

Better. So we have, you know, we have avelomab, which is FDA approved to treat microcell carcinoma. And so it doesn't necessarily work better. They've just sort of been looked at in different tumors.

[A]

Okay.

[B]

Okay. So this was again, these are, you know, it's hard to enroll people to these studies. So it was, it was an open label. So study group one was metastatic cutaneous squam, 78 patients. Group two, locally advanced, 31 patients. The dosing is basically 800mg IV every two weeks. But then there was a metastatic cohort that went on to get 1200 every three weeks. So just, you know, IV dosing every two to three weeks is sort of for us to think about.

[A]

Did these people get less of the side effects?

[B]

Can I finish giving the results?

[A]

Sorry, sorry, sorry.

[B]

Okay. And then we could talk about that. Matt. Okay, Most people were treatment naive. So object, primary endpoint, objective response rate and duration of response. Okay, so what were, what were the objective response rates for metastatic? 50% had a CR or PR and 12.8% had a complete response. So like all their tumor gone. And for locally advanced, 54.8 had a objective response and then 25.8% had a complete response. Durability. Median duration of response was not reached in either. But it was estimated for metastatic that the probability of maintaining response for at least 24 months was 72% and that that was about 80% for locally advanced. So I don't know exactly how you estimate that when you don't have it, but that, that's, you know, that's it. So that's what they found. So those responses actually tended to deepen over time. And so they, you know, patients had higher response rates, you know, as with extended follow up, than they did at their original interim analysis. And so that was kind of it. That was interesting. So, you know, this is really not like drug works while you're giving it. It's drug induces immune response. Immune response works even when you're not on the drug. So PD L1 status. A lot of times when you look at these immunotherapy studies, they look at PD L1 status of the tumor and you know, there was not a. Did not. Clearly it wasn't like, oh, only high PD L1 expressors responded and low ones did not. So that was kind of interesting. And you know, so kind of the take home, about half of people are going to respond and if they do, that's probably going to be a pretty durable response. So what about safety? You might ask Mask.

[A]

Okay, yes.

[B]

So if you looked across there, you know, adverse event rates were like 94% of grade 3 or higher. AES and immune related adverse events were about 27% but only about 3.6% of these were grade 3 and there were no grade 4 immune related adverse events. So that was kind of interesting. So if we, you know, that is, that is, that was higher in the other studies. So if we look at like Simiplumab, which is a PD1 inhibitor, the, the grade 3 or higher immune treatment related adverse events have been like about 20%. And if we look at pembrolizumab, those rates were severe. Immune related adverse events were about 8 to 9%. So you know, and their, their efficacy, objective response rates were in the sort of 50ish percent range. So really what we're seeing is that the, the biggest difference is lower adverse event rates with the PD L1 inhibitor cosabellumab. So that similar efficacy maybe lower kind of late, higher grade adverse events.

[A]

Huh. Does, does it ever make any sense? Does anybody ever get both a PD1 and a PDL1?

[B]

I don't know. You don't do that. That's just not a thing that is done. But you know, it didn't seem like it would be what it mean. Could you go from a PD one so they don't, you know, when we talk about switching drugs in our podcast or things like psoriasis or ad, you know, we have lots of conversations where we're like, like yeah, I mean they're not responding to geselkumab, so I'm going to put them on rhizakizumab and we switch between classes all the time. They don't tend to do that in oncology. I think what will be interesting to see is how much switching happens from a PD1 inhibitor to a PD L1 inhibitor.

[C]

If a tumor does not express PD L1. How in the hell do these Drugs work.

[B]

I mean, so there's a. There's a lot of la. There's not a lot of standardization of how you measure PD L1. And it's really. Are they PD L1 low versus high? So I think that in general you can find PD L1, but one, there's different ways to measure it. It's not standardized. And so, you know, what is called, what's considered a high response? A high expressor. Is it greater than 5%? Is it greater than 2%? How are you measuring that? So I think that that's. So it's really not. Are you zero. Yes or no? It's low or high?

[C]

I mean, if I had a squam and they were talking to me about their therapies, I would do the PD L1. Like, it just makes way more sense.

[B]

It does seem to make more sense. Yeah. I mean, so the question is like, you know, it'll be interesting to see if we have longer term data or head to head data. Does one work better? It's probably hard to power that study.

[C]

Yeah, like the hepatitis, the colitis, the endocrinopathies. I mean, those are horrible side.

[B]

Those are the horrible side effects. Yeah.

[C]

Huh.

[A]

What if you combined one of these drugs with those immune stimulatory herbs that you talked about that make dermatomyositis worse?

[B]

You could have really bad dermatomyositis.

[A]

Seems like that would. That'd be a knockout. You'd be guaranteed basically to be cured of your cancer.

[B]

There you go.

[A]

Immunostimulatory herbs.

[B]

Dermatomyositis. Yeah.

[C]

Right.

[A]

Andromatic. So you get dermato, but your cancer's gone.

[B]

Yeah, but no, I thought it was important for us to know about this. It is an FDA approved drug for the treatment of metastatic and locally advanced squamous cell carcinoma. It's a little different mechanism of action. A PD L1 inhibitor. Cosabellumab. Just be on the lookout for it.

[C]

So simiplimab and pembro have the same indication. Locally advanced and metastatic, right?

[B]

Yes, locally advanced and metastatic.

[C]

Cimeplumab has that adjuvant approval too. Right.

[B]

After resection and radiation in the adjuvant setting. Simiplimab is FDA approved. Pembrolizumab is not. This cosabellumab has that. I'm aware of no studies looking at it in that setting. All right.

[C]

Just a little overall review for our people interested in PD1. PD L1.

[B]

Yeah.

[A]

Fair. All right, Patton, what do you got?

[C]

All right, my second six pack Was from December. Jamaderm titled A novel tool for predicting malignant disease in adult patients with dermatomyositis by Yay et al. So 2023 International Myositis Assessment and Clinical Studies Group. They put together that little algorithm. We covered it in an earlier episode, I'm sure everyone remembers. Stratified dermatomyositis patients into low intermediate high risk groups and then it made screening recommendations. So for that assessment, there were a lot of different factors, right?

[A]

Would.

[C]

Do they have dermato. Do they have. I always call it cutaneous only. I know it's clinically amyopathic, but cutaneous only is easier. Certain antibody profiles. If you had interstitial lung disease, there were just a lot of different factors. And then you put people into low intermediate high risk and they gave screening recommendations. This study was just kind of that but narrowed down things a bit. Retrospective study performed at one institution in China. Training was done on cases that were done in the Department of Dermatology. And then they did an external validation that was done on 262 dermatomyositis patients in the Department of Room. Criteria they came up with, they called it the TIP CA model. So T is for anti TIF1 gamma antibodies I interstitial lung disease P poikloderma C clinical diagnosis where they had DM or cutaneous only DM and that was it. No. And anemia. And so it was like you get one point or zero points. Basically, if you have any of those, you get one point. The exception being interstitial lung disease. If you have interstitial lung disease, actually that gets you a zero. And if you don't have interstitial lung disease, you get a point. This was a little bit weird in the table. That's how they scored it in the abstract. It was like if you have interstitial lung disease, you get a minus one.

[A]

Minus one. I saw that.

[B]

Yeah, it was the one protective factor.

[C]

It was. But they just, they, they did the math differently. They called it minus one in the abstract, but in that table they're like, if you didn't have it, it's zero. And if you, if you don't. No, if you have it, that's protective. You get zero. If you don't have it, you get a one.

[A]

It's not either a zero or. So it could be a zero one or it could be a zero. Negative one.

[C]

No, I, I don't need. The abstract in the table were different. That's all. It was like a. Almost like a. Maybe they'll publish a Neuratum. Because they say if you have a score of five. Well, if you, if interstitial lung disease is either minus one or zero, you'll. You'll never get to five. So I think it's zero.

[A]

Let's just go with 010101.

[C]

And basically, if you have dermatomyositis and you don't want cancer, then you'd rather have interstitial lung disease.

[B]

Yes, yes, yes, that's it. Except that sounds kind of lousy as well.

[C]

It. Yeah, neither one's good. All right. So it's kind of an easier thing to use, I guess, than that other table. They used a cutoff value of 2.5. So if you were one or two on that little table, then you know that's below. And if you were 3, 4, 5, they used that. In the validation cohort, sensitivity was 82%, specificity was 66%. So pretty sensitive, but.

[B]

Right.

[C]

Specificity takes a little bit of a hit. The authors didn't really go into what screening do I do for a patient with three, four or five. So that was kind of left open. The features of the TIP CA model that aren't really in that earlier algorithm were poikiloderma and anemia. So maybe just do the ICAMS model and maybe add anemia and poikiloderma. I don't know. I. I just. It jumped out at me because, hey, we have this cool tool. It's pretty similar to that ICAMs. And I think the ICAMS is just a little bit more thorough. And what's nice about that paper, 20, 23, they actually go into, here's your screening for low risk, here's your screening for intermediate, and here's your screening for high risk. So a little bit more of a complete panel. I don't know if this adds much.

[B]

Yeah, I thought it was a good refresher of what is a risk factor versus a protective factor.

[C]

Yeah.

[A]

So basically, Patton, this was the cheap Chinese knockoff of the higher end original brand name tool.

[C]

I don't want to get into any of that.

[A]

No. Useful though, because it is such a. What's always interesting to me. And I guess they, I think of duration of dermatomyositis is such a big part of it. Like whenever I see a new clinically in myopathic dermatomyositis patient, I'm always like, how long have you had this rash? And if they've had it more than two years, I'm like, ah, you're fine. You don't have cancer. And if it's less than two years. I'm like, we gotta think about it. And that's when. So I'm just interested. That duration of disease they did doesn't, doesn't play into these.

[C]

Yeah, it wasn't, wasn't for that other one either. That icam. They don't factor duration.

[A]

Yeah, it's interesting. It's interesting.

[C]

You just. That's a mental thing because if you're like, well, you've had this for long, if you, if it was associated with.

[A]

Cancer, you'd be dead by now.

[C]

Diagnosed already. Yeah, exactly.

[A]

Yeah, that's exactly it. Just. And it has been in an article, it was in a guideline or a recommendation somewhere that like for the first X years you should be, you know, screening these people. And then after so long, you didn't need to keep screening them every year. Okay, I think that's where I came up with that somewhere. All right, so get it on my last one more.

[B]

Matt, you're, you're cut off.

[A]

You got one paper, the one barely counts. It was basically that like people who go on Lotus oral Minoxidil, essentially all of them, if they are a man, get hypertrichosis on their arms, but they don't care. And that was, it was 5 milligrams a day and it was men. And like I said, essentially all of them got some. Not even essentially all of them, all of them essentially got some element of hypertrichosis, especially if they were under the age of 41. So just interesting, that might be something worth talking about to patients. Whenever you're starting them on low dose or minoxidil, your body might get hairier, but quality of life didn't, didn't affect it at all. The much more interesting thing, and this is the big medical legal risk for dermatologists and maybe everybody else in the world of derm knows all about this, but I had never heard of it. That there is now like a very specific warning from the FDA about using Bactrim in young healthy people. That there is every time you prescribe Bactrim to a young, healthy person, if it's for more than seven days, there is a 1 in 3,000 chance that they will die from acute respiratory failure. And it is specific to young people. Now they don't know if it's specific to young people because young people are the people who get longer courses of Bactrim because they're getting it for acne. So this has been specifically associated with Bactrim for acne. And so maybe older, you know, if it's for a UTI or a flick, you know, whatever. An infection, maybe you only get a seven day course, whereas if you're getting it for acne, maybe you get a three month course. So you're more likely to get it. But it's a very specific lung injury, unlike normal lung injuries from other things. And it's 1 in 3,000. And this was been reported from a bunch of cases from one of the children's hospitals here in America. This was a Canadian large database study. And the attributable risk is about 1 in 3,000. They compared it. Your odds of getting this lung injury after getting amoxicillin, your odds of getting it after a cephalosporin and your odds of getting it after Bactrim. And one in 3,000 people more got it after Bactrim compared to the others. And so did you guys know about this?

[B]

Yeah, they controlled well for baseline risk for people getting in. It wasn't like. Well, because they all had lung infections like they controlled for that. Yeah, this is really important. I hate Bactrim as like a drug for acne and I'm always happy to have a reason not to give it. And so it's very important to me for that. But no, I think people sometimes give this out a little too loosey goosey for, for acne when we do have other options. And so I agree people need to counsel patients and say, you know, there is this risk and maybe it'll also help patients not to be like, I'll just take the antibiotic.

[A]

Yeah, I mean I, I'd say where I probably use it the most is, you know, community acquired mrsa. I almost always use doxy, but I, you know, I think Bactrim probably works a little bit better. So sometimes for skin infections or hs, I'll use Bactrim. And this may make me think of Backdrum as more of a last, even more of a last line option than it already was because of Steven Johnson and 10 kind of stuff.

[B]

Right. And this is actually a way higher risk than Steven Johnson or 10.

[A]

Seems like it to me. I mean 1 in 3,000 seems like.

[B]

A. Yeah, I mean if 1 in 3,000 people we treated with doxycycline got Stevens Johnson or you know, or even with Backtram, it's a. Yeah, that's a much lower risk. This is a meaningful real. Right. If you. Thank you for bringing that to our attention because you off right.

[A]

If wolf. And if you think about it, if you're a derm and you prescribe Bactrim twice a week. That's going to be 100 times a year. If you have a 30 year career, that's going to be a 3,000 people. You will kill one person from this reaction. If you prescribe actor twice a week.

[C]

For your whole career.

[B]

We should just go back to chloramphenicol. That was, that was an old time acne drug.

[A]

But I like it.

[C]

I just thought about this now because I barely ever give Bactrim. I give a ton of dapsone. Is this Bactrim specific or sulfonic? Did they look at other sulfonamide antibiotics?

[A]

Dapsone did not come up as I was digging into this.

[B]

I see a trinetic study in your future.

[C]

Oh, I love dapsone. Don't take it away.

[B]

All right.

[A]

It'll be okay.

[B]

We'll report back. All right.

[A]

Well, I want to thank everybody for joining us this week. We hope you learned a few things. Hope you laughed once or twice. And mostly we hope you're planning to join us next week. Until then, I'm Matt Zyrus.

[C]

I'm Tim Patton.

[B]

And I'm Laura Faris. And we are derms on drug.