[music] Welcome to Derms on Drugs of Video Podcast brought to you by scholars in medicine, the best educational platform of dermatology and provided at no cost to medical providers. Derms on Drugs is where cutting edge Derm meets at our Miss Comedy. Matt Zeyer, C.H.E.T. We come to him in a residency buddies, Laura Ferris and Kim Patton to use our 60 years of combined 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 you'll have some fun listening. New episodes drop every Friday on scholars in medicine, Apple Podcasts, Spotify and other major podcast platforms. The video component for those who haven't checked it out has the key figures and tables from the articles we talk about. The episode description also has a link that will get you to the links to the articles and any other resources we might discuss on the episode. So let's go ahead and get into it. This week we have got a fantastic episode. We are going to do a deep dive into Bulless Pempfagoyd and then we are going to be joined with our expert guest, Dr. Donna Colton from the University of North Carolina. I'm going to lead us off with an article that fortuitously just published in JAD that was a clinical review on Bulless Pempfagoyd. And really this is me just hitting some of the highlights of Pempfagoyd kind of a quick review for anybody who hasn't seen a case recently and really thought it through. The key things from this clinical review is to remember that 20% of people have no blisters. You can have mucosal involvement in up to 30% of patients and mucosal involvement is usually a marker for worse disease that's going to be harder to treat. Itching can precede blisters by months, but if itching is caused by Pempfagoyd, if you do a biopsy, there should be a positive DIF or surrology. It's an interesting question that will kind of get into a little bit is do we think that's under diagnosed because you know when I if I see somebody who's itching, if they've got red blotches, I'm likely to biopsy them, but if they don't, I might not. We've got drug induced Pempfagoyd, the big drug, the hot thing causing that or the dipeptidial peptidase for inhibitors or the glipthens and spronolactone those are apparently the two most common drugs tends to be younger patients worse blisters, good response to therapy. One percent of people who are on immune checkpoint inhibitors can get a induced Pempfagoyd can be bad enough that you need to stop the drug treatment still necessary as it may not go away once that genies out of the bottle. And then what drug induced you whether it's a dipeptidial peptidase for is brinolactone and I'll be interested to hear what our guests and my co-hosts have to say you don't want to treat gently hoping it'll go away you treat for real, but you try to stop sooner if they're going great after they've discontinued the drug. And then the last thing for each and e for the biopsy you want to biopsy either an entire intact blister or the edge of a blister then for the immunofluorescence you want to biopsy non bullies inflamed skin within a couple centimeters of a blister now one of the questions and I'm going to have for. Our guest and in my co-hosts what if there's no non inflamed skin next to the blisters what if it's just the blister just biops right next to it I guess and then we should whenever we suspect the diagnosis or after we get it be ordering utilizes for BP 180 and BP 230 might use the indirect immunofluorescence if you've got a weird case, but you need a good lab if you're going to do that. Those were the kind of the not going to really get into the treatment because we're going to talk about that at length as we go forward, but Dr. Patten fairs anything else you guys want to add that is kind of big big big picture stuff for the list of Pemphagoid before we move on. Those are good points it so remind us which are which issue of the jad was this review and I looked at it quickly but it seemed like a great resource for people like me who don't treat this every day. It was just published June of 2025 and Dr. Colton our guest was one of the authors on the paper great thank you. Yeah I thought that was a good review you may have said it one of the things that always stands out to me with the I mean check point inhibitor therapy is that could be several it could be like a year or even two years after that medication is discontinued so there can be a pretty significant delay on that I see I induced is that I mean would we even really consider that I see I is in a just possible that an old person got Pemphagoid good question. Yeah hard to hard to know hard to know I think if you did one of those see for the DPP for inhibitors what's that time. Like that's a good question because I I mean I'll be interested to see what Dr. Colton says with DPP for inhibitors I mean some of those patients honestly have been on DPP for inhibitors for years. I think of I think of that less like a OES this medication definitely triggered it as opposed to you I mean maybe a triggered it but you're on this DPP for inhibitor there's a reason why that could make the Pemphagoid more difficult to treat so we should get you off it regardless. But a fair number of times it's it's not like hey discontinue the med and then you don't need to treat I have found that you know if you get lucky you discontinue the med and they get better but a lot of those patients need treatment I think if you kept them on the DPP for inhibitor that treatment might be a little bit more challenging might have to be a little bit more aggressive. And the problem is that it like molecularly mimics the NC 16 a domain or something like that correct. Oh I don't think so no I my understanding is the DPP for so it's a dipeptal peptidase. They inhibit that those dipeptal peptidases they break down things that are important for if you inhibit it you get these proteins that help you manage sugars but things like EOTaxin are also broken down by the dipeptal peptidase for that enzyme. So what you're inhibiting is there are more things that DPP's break down that maybe have nothing to do with diabetes but they could play a role in making BP more active EOTaxin is like the big one I think there's another site of kind CXCR one of those guys that it breaks down and by not breaking that down that could contribute to kind of the inflammatory meal you that you see with B. Interesting okay let's let's go ahead and move on to our second article that the fairs what you got okay so I have actually a recently published paper in the journal of dermatology. I'm sure I'm saying that wrong at all so this is effectiveness of de pili maub and omelism ab embolus pump a good a nationwide retrospective cohort study so this is basically a retrospective review 58 patients with BP. They actually did include you know patients who had check plan and have your glipid and associated BP so this is sort of more real world versus what you might see in a clinical trial and so about two thirds of these patients ended up being treated with de pili maub and about one third with omelism ab and so again this was not randomized this is retrospective overall the omelism ab group seem to actually have a little bit more severe disease so longer duration higher BP. D.A.I. sort of one of the outcome measures of BP higher titers higher DLQI more prednisone at baseline so the primary outcome that they looked at were proportion of patients who had disease control within eight weeks and then at the end of follow up and they called that like no new lesions no paritis all the existing lesions that they had were healing and then they also looked at things like complete or partial remission on minimal or no therapy so you know overall what did they see the de pili maub group actually seem to do a little bit better so their disease control rate was a little bit higher about 56% versus 27% and at the end of follow up it was higher like 90 versus 78% and little bit of lower relapse so you know kind of their take on point was well de pili maub did a little better than omelism ab but the omelism ab patients were a little bit more severe the other thing that was interesting was that like most people in this study were on concomitant medication so if you look like 80 and the only issue per cent of them were on in the in the omelism ab group 83% were on systemic steroids versus about 60% in the de pili maub group and most you know a lot of them were on topical steroids there was some at the state some like a phenylate mafatil so you know I thought this was good because this is to be honest probably how we're going to use these drugs in the real world is not as monotherapy we're going to use them. So it would be nice to see like a little more quantitative answer as to what minimal therapy means or you know to see a little more ability to quantitative things like how much was your steroid dose
reduced, how much was self-sept reduced, but that's also harder to do in a retrospective setting. So it's not like Zollare is being pursued for Pemphagoid as a indication, correct? So there's not really like the idea of comparing the two of them, you know, Zollare's never going to be, we're never going to be in a situation where you're like, "Well, should I start him on Dupier? Should I start him on Zollare?" Because the Zollare's going to be next to impossible to get in the zoo, and the Dupier will be less impossible to get, but still difficult. Is that about right? Yes, I think that given the new indication for Dupier Mab, which just, you know, came out, I can't imagine a world in which you would say, "What should I start with? Should I start with Zollare or start with Dupixen?" But I think it's helpful to understand how this works in context, because as we know with these complex diseases, even things like psoriasis, you can have a great biologic, but not everybody's a responder. It also would, you know, suggest that like that might be a good second line, and then again, realize like these were patients who were treated years ago before we had an indication for any of these. Worked in, in the long-ish term, worked in like, if you put together the complete remission on minimal therapy and the complete remission off therapy, worked in like 90% of people. So then the question is in the real trial, how ordered it work, and that hasn't been published yet, but we're going to talk about it for sure. But Dr. Patten, why don't you tell us about how the Dupier Pempfagoid trial was set up? Yeah, okay. So I will, my deep dive paper was from advances in therapy, titled a study design of a phase two, three randomized control trial of Dupiliamab and adults with Bulls Pempfagoid Liberty-BP adept. It was published last year, lead author, Mural, fair number of regeneron employees also as authors that outlined the protocol that was used to evaluate the efficacy of Dupier and the treatment of BP. Design is pretty straightforward. Patients had 35 day pre-screening period. They had to be off-moderate to potent topical steroids and or systemic steroids for at least one week. And then everybody was given a systemic steroid regimen for four to six weeks. The initial dose of the steroids was based on the severity of the Pempfagoid and also if they initially didn't respond to that initial dose after which, you know, so they started both the steroid and the Pempf and the Dupier at the same time. Yeah, steroid do be starting week zero. And if they had placebo and if they had bad disease, they started higher steroid. If they had not terrible disease and they didn't get better quickly, then they got the high-urdo steroid. That's correct. All right, and then they were on the steroid for how long? Four to six weeks, you had to reach a certain period before you could start to taper the prednisone. So, you know, the original design was at that six-week period you start, but based on how they did it, there were some patients at four weeks where they were able to start tapering the prednisone with the goal of being off steroids by week 16. We already said half the patients received Dupier in the same manner that Dupier is always given, the loading dose and then 300 milligrams every other week. Primary endpoint was the proportion of patients in what they called complete sustained remission at week 36. So, there were three things that you had to meet to meet that criteria. You had to be off steroids by week 16 with no clinical evidence of disease activity. You had to go without relapse or the need for rescue therapy through week 36. So, that's three things. The taper of off of steroids with no clinical evidence by week 16 and then no relapse and then no need for rescue therapy through week 36. So, basically, you had to be completely tapered off of systemic steroids and completely clear by week 16 and then you had to stay completely clear with not needing anything else out to week 36. And it's kind of weird. So, when you look at you had to go without relapse or need for rescue therapy, well, why else would you give somebody rescue therapy if they didn't relapse? So, isn't that kind of the same thing? But you could have maybe disease activity flare up. That wasn't as bad. It didn't meet the specific definition for what they called a relapse, which I don't really want to get into now. Maybe when we bring Dr. Cole, now we can talk about that. So, right. Yeah, that's pretty much it. So, could you have a little flare that didn't require rescue therapy? Yes, could you give somebody rescue therapy even though they technically didn't meet relapse, right? So, if they got really itchy, for instance, and you gave them rescue therapy to treat that itchiness. Technically, that isn't a relapse, but you did give them rescue therapy. So, they are a little bit different. Okay. All right. So, yeah, inclusion, exclusion, criteria. I mean, the list of that is all in the paper. Pretty straightforward. You know, relatively, I guess moderate BP, it was a BP die of 24. Now, the highest you could be on a BP dies 360. So, it's nowhere near like the worst of the worst Pemphagoid, but I think it would have been hard to do that to bring in those sort of severity of patients. But, yeah, that's pretty much it. All right. So, reasonably complicated, right? To put it that way, but that's pretty complicated for a normal clinical trial compared to just randomized double-blown placebo controlled for the first 16 weeks. The idea that there was the steroid running and then the steroid taper, it's interesting. It's interesting. We've never seen a trial in Durham designed like this. We almost always get monotherapy. Yeah, because I think to Regeneron's credit, they didn't want patients to have Pemphagoid that was, you know, let's say, doobie didn't work at all. Then you have untreated Pemphagoid patients in a trial. And you just can't do that with Pemphagoid. Those patients can wind up in the hospital. So, how do you evaluate a drug when you're also giving it with what is a very, very effective medication that is prednisone? All right. So, after all of that lead up, let's get our guest in Dr. Donna Colton. So, Donna is faculty at the University of North Carolina, where she runs a blistering disease clinic and is very active in the blistering disease world as well. We all just had the pleasure of hearing her lecture at the Maui Dermand PPA meeting. So, Dr. Colton, great to have you on the show. Yeah, so glad to be here. And I have to throw in Dr. Colton also runs the clinical trials, is the co-director of the clinical trials unit, the University of North Carolina. And she also runs the immunofluorescence lab. So, I think one of few dermatologists who actually run an immunofluorescence lab, which is kind of a problem. Wow. Yeah. I'm impressed. Very diversified. Yeah. I am impressed. So, Dr. Colton, were you an investigator in the dupe Pemphagoid trials? I was. All right. So, I think probably the million dollar question, maybe the billion dollar question that we all want to know. So, what, you know, the data hasn't been published in a peer-reviewed format yet. So, how else will work? That's what we all want to know. Yeah. So, I think there's how well did it work in the study? And then there's how well does it work in real life? And I would say, you know, some of people have been using it off label for years now for Pemphagoid. Access is really difficult. So, if you are able to get samples, maybe that's something that you can do off label, we do not have samples. And so, I've not really had the experience using it before this study. And so, but I agree with kind of what's been talked about is the way the study was designed is everybody started on prednisone. And the idea with everybody should get to a disease control on prednisone. And then the prednisone taper would begin and hopefully Dupy would hold people in a state of disease clearance or disease remission. And so, you know, in real life, we know there's going to be little trip ups along the way. The way the study was designed, there could be no faltering. Like, everything had to go perfectly. You know, they had to reach disease control. The taper had to begin. They could not go backwards on the taper. So, as they were tapering down it, they, you know, could not have a relapse. They could not have to go back up on the taper. So, everything had to go perfectly. And because of that, the endpoints were super strict. And so, the press release that we have, the numbers of Dupy success, where I think not as high as we would expect based on some of these real world case series and reports and retrospective reviews that are out there. And so, I think that's the difference. So, I think Dupy is going to be super helpful. And would love to hear, you know, you guys experience especially, Tim, your experience, because I know you treat a lot of these patients as well. But I think in real world, it's going to perform better than what we saw in the clinical trial, at least in the press release results that came out. Yeah, my initial experience with Dupy, and I think it was just a factor of
being a referral center is I think people were using it off label people were able to get their patient samples or were able to say maybe there's a component of a topic dermatitis because I did a biopsy and there was some sponge germ and you know you could you could make an argument okay there's a component yes they have BP no question but maybe there's a component of a topic dermatitis that is making this a little bit harder to control I think I was just a occasion to get it covered by insurance but I saw a lot of patients with bad disease who had been on Dupy that makes sense I started talking to community dermatologists and then I started to hear these anecdotal reports of excellent disease control with Dupy so it was a there was like I was getting two separate sort of personal experiences yeah I'm a little bit worried you know I actually heard a lecture the other day about Dupy and BP and somebody saying well this is great because of course we'd rather use Dupy than steroids and that's what I'm a little bit worried about is that that was not it was not with the study looked at right this was Dupy in conjunction with steroids and that's what the end points of the trial were so what we can say now is you know Dupy while giving steroids may give us these these particular end points that are going to help us manage these patients but it's a very sort of specific you know regimen that this study looked at and I think we're going to just figure out from real world experience how we're going to use Dupy you know are we going to give it to every BP patient are we going to to the patient who just you know do we treat with monotherapy prednisone and not add the Dupy right away where does retuximab play because retuximab I can get covered I don't know what it's like in North Carolina but I can get retuximab for BP patients and if that offers us you know decrease in antibody titers but more higher percentage of patients that actually reach remission because those titers are gone and we can get them off prednisone where's Dupy going to fall in if we're able to get our patients retuximab I think it's going to be really interesting I'm glad we you know having medication that is FDA approved I think it's it's pretty exciting I'm curious to see where we go from here so Donna how are you going to so next you know Pemphagoid you know we'll call it as close as you can get to run to the male Pemphagoid so you know good number of blisters but they're not like oh my god I have to send it to the hospital what are you you know what is it prednisone plus doxinia cinamide and then in topical steroids and seeing back in six weeks take like what are you going to be doing what are you going to be doing I mean we're all trying to figure out where Dupy's going to fall in our treatment algorithm and I think right a lot of us feel like it is what you just suggested I think is pretty reasonable right so maybe somebody comes in with relatively mild to moderate but on the lower end of moderate you might try doxinia cinamide first but I think I'm going to have a low threshold to just go ahead and start Dupy first line because I and maybe it's a referral bias a lot of the patients I get have not responded well to doxinia cinamide so I get them after that already hasn't worked and so maybe out there in the real world like it works pretty great I'm only getting the people who didn't work for um and but but I you know if patient has needle phobia or some other reason why they don't want to be on Dupy but my guess is I'm going to start trying to get it first line for patients you know if they have disease that is beyond what topicals can handle and I probably will unless there's some major contribution use of with steroids as some sort of bridge um you know I I again I don't know how it's going to work if you just did Dupy without steroids I agree with Tim like that's probably it you know it's not how it was tested and even in the real world studies that are out there they're almost all on steroids as well um so it might be one of those drugs that can like hold it once it's cleared with steroids but you know we I don't know that we know can it can it do all the work from the keko well what are you guys go ahead Matt go ahead first I'm able to tell from the data like once they sort of have the final publication like you know like monotherapy is not how we treat most complex diseases right so basically the minute that you couldn't come off or continue to taper your prednisone you were a failure end of story like are we going to be able to tell like what if the Dupy group had like half of the the cumulative steroid dose that would be like a pretty meaningful endpoint but are we going to be able to see that do you think from the data that were collected I do think that data will be there I think um I think it scores right like a huge thing and steroids help with itch too but you know we know Dupy's going to help with that and so I think you know again in real life am I going to slow down the prednisone taper if I need to yeah I will um while we give do be a little more time but I think everybody's angle is always going to be to get their patients off of corticosteroids um would we tolerate a lower dose of corticosteroids we would probably right like if you could get them down to five milligrams a day is that good with such as safety because we haven't really been touched on safety right so it's such a safe drug um you know I love methotrexate I am a methotrexate band and I use a ton of it and I reenly dose it in patients with reenl disease like I I'm not afraid to use it um and I think it works pretty well but there's no comparison when it comes to safety it's kind of how I feel about it with Dupy so I I'm going to be transitioning over and might I throw a little methotrexate in there maybe I might do that um so we'll see um but yeah I know I think well I think we'll have some of that data will be really interesting to see again the you know the study was not designed to allow people to stay on a low dose of prednisone or serage just because we had other studies and autoimmune blistering where that allowance of somebody to stay at five milligrams a day it it mass the difference between the treatment and the placebo group turns out five milligrams a day can hold a lot of people um yeah if you sleep for slowly enough you take for slowly and I you know in clinical practice I don't know to know how you've had the experience but I I don't get nervous in the beginning of the taper I get nervous at the end of the taper and I will always say the five milligrams some is the glue that holds it all together and you might think it's nothing and then you and then you just stop it and then the blisters come back so I you know I've seen that in practice I know I love when the new residents come in and they're like five milligrams is sub physiologic so we're actually not giving them anything I'm like trust me I know I know right that's what we learned uh right but don't you have the three milligram patient the two milligram patient yeah I mean that seems sub therapeutic but right they they they forget to refill it and they call you and they're like I'm starting to get it to you and I have a hive and maybe one of these is a little blister it's it's very odd do you guys start at you know generally start everybody at 40 and tell them stay on this until your blisters are all healed and then like wait do you just say start on 40 stay on it till you come back in a month like what do you how do how do you do the prednisone yeah it's tricky I I do base it based on disease severity so I'll go higher in a patient that has more severe disease um so you know closer to um white bi mix per gig if they're more moderate disease um but but a lot of times you know I I my goal is to get patients mostly clear on the prednisone high dose prednisone before we begin the taper so I think my pet peeve when we're talking about like training the residents is they want to go ahead and like prescribe the taper and I'm like we don't know when the taper can begin each patient is a little bit different and we have to kind of let them get there now the other thing that can change the game is if the patient's like I'm miserable and I hate you because you put me on this terrible prednisone get me off then we'll taper before maybe their disease is clear but otherwise I really like disease to be at least disease control right so I know we talked about not getting into the nuance of disease control disease remission but like it they just have to not be getting new blisters and most of the old blisters have to be healing um whereas you know remission would be no blisters at all so I don't wait for that but I do wait for a disease control before I start to taper it does not always go that way plenty of times you know we see them back and they're like no I'm still on my pred 60 and they're totally clear they've been clear for weeks and it just you know it doesn't always go as planned but that's the idea I don't know Tim how do you do it yeah same exact way I would say 20 to 40 for most patients you know the older and frailer they are maybe the less severe disease sometimes 20 milligrams honestly we'll shut it down like they come back in two weeks four weeks and they have no active disease uh but 30 to 40 average and you know with the most severe patients fair number of times they're they're heading to the hospital they're covered in blisters they're in really really bad shape and that's when you can give IV you know 80 milligrams of solute med draw Q8 hours like high dose steroids really do shut down the disease you just couldn't keep them on it for more than like five days I mean those are the patients where after three days then we'll we'll transition them to PO and maybe with that initial severe presentation you're just going to get them retoxamab while they're in the hospital can you talk about what your taper looks like after I think that's one of the things with with the little bit that I treat that I've learned is like you can't be like
We're going to taper you by 10 milligrams a week. Can you talk about how slow that taper should be? I think it really probably depends on vibes. Are we allowed to say that? Are we? Yeah. We actually have a lot of vibes. No, but you kind of have a sense of somebody who is at high risk of relapse. Once they're in disease control, I think you can go down by 10 milligram increments until you get to 30. And this again, just how I was trained, we all trained a little bit different. Once you get to 30 and get maybe you're only starting at 30, but then I go down by 5 milligrams in there. I think one of the teachings is that you should be doing every other day, tapering. And I find that just incredibly challenging for these older patients. And more often than not, they come back, fall mixed up. So I have not been doing that as much. So once I'm at 30, then I go down by 5 milligrams. And I, does anybody remember Calvin and Hobbs? Such a great cartoon from back in the day. And they played Calvin Ball, which they just made up the rules. I feel like that's kind of what we do with prednisone tape sometimes. Is it by every week? Is it by every 10 days? Is it by like, we try to make these nice round numbers. But really, we're just following the patient. You just don't want to do it so fast that you miss the flare coming. It's kind of what I think, right? You don't want to like pull the rug out from under them. And they think they're doing great. But really, you just missed what 10 milligrams would look like. You just went so fast. You missed it. I don't know if you agree. Right. No, I agree. And I think when you're saying 10 and 5, you're talking like every two weeks, sometimes with the lower doses, I'll go month or months, right? If they were really bad and you just don't want to get them back to that period where they flare, if they get down to 10 milligrams and they're clear, you know, sometimes in the patient that had a bad sort of experience, you just say, you're going to be on 10 for the next two months, maybe three. 10 milligrams patients do fine. And I always notify the piece, private care physician when I start this, like these patients are probably going to be on prednisone for the next several months. You know, shoot me a message if you need that taper to go quicker because of, you know, sugars being high or blood pressure being more difficult to manage. But like not one single time has a PCP called me and said, it's got to be quicker. They just manage that stuff. Andrew, it's in it's, I feel like it's one way or the other, either that patients take the prednisone and they want off and then there's the patients who love it. And they're like, I mean, I don't see the problem. I'm just staying on this forever. I'll keep that prednisone 10 forever. I never felt better. Yeah. I have more energy and my knees don't hurt. Yeah. No, they kind of get mad at us when we try to take it away. You're like, but it's really bad long term. No, I, you know, I think exactly what you said is is we're all trying to go for less, less prednisone always. And it just sometimes you got to go a little slower for these, for these older patients. Have either of you gotten this now like through insurance, you know, had a BP person come in. I know like it just got approved like days ago, but or maybe a week or two ago. But has anybody, have either of you actually like gotten the approval and how hard was it? So curious. So I got, we actually had a few approvals before it would, you know, before it was, we forgot the indication. And it always surprised me because I was very pessimistic. The resident would be like, I'm gonna first cry and do be as like, we're never gonna get recovered. Good luck fighting that. But, but sometimes we would get it like with just only both Pemphagoid as the associated disease. So no, Pregor nodularis, no, you know, etopic dermatitis in the background. We didn't link it with any of those and it got approved. So I'm hopeful. I think, you know, if you think about retoxin map for Pemphagus, initially, payers were covering it. There were very few hoops to jump through. And now actually I'm starting to see some of the hoops with their, you know, you can only have this much in this period of time and we're having to like write the appeal letters and explain the data. So I, who knows what the trajectory will look like for this if we'll have, you know, good access initially and then some roadblocks or maybe the roadblocks will come sooner. I don't know. Uh, yeah, it's been very hit or miss. I swear there was a period of time where it looked like they just were going, the insurance companies were just gonna cover the med. And then I would say the last three or four patients that I tried to get it for with just the bullies Pemphagoi and indication they, they denied it. Yeah, we'll see. It'll be interesting. I, you know, we were talking about like you with Praggon Agilaris and you have to have 20 nodules or like a type of dermatitis you have to have failed X, Y and Z. Like, it'll be interesting to see what, what we have to do. Yep. All right. So Donna, let's, let's kind of change directions a little bit here. So one of the questions comes up all the time with bullies Pemphagoi is where do you do the D.I.F. And I think we all know, right? If it, if they've got a blister and they've got red skin next to the blister, you do the D.I.F. from the red skin right next to the blister. But you see some of these people who really all of the red skin is blistered. Uh, and it's just, you know, blister or normal skin next to a blister. Where do you do it in that person? Right. If they're all blistered, then I go for the normal skin right next to the blister. And is that just as sensitive to you think as, you know, the, if they've got some red skin and you buy up to the red skin, or do you get, you're, you worried you're going to miss the diagnosis if you're biopsy normal skin next to the blister? I'm not that worried. I mean, the antibodies are not all that smart, right? They're not like drawing a line in the sand and they can't go past it. I don't know. I think I, you know, there's that positive feedback that I get when I do biopsy and then I like, I'm reading my, my own D.I.F. and I'm like, well, that was a little close. Um, but you know, you just need some intact basement memories. And that's really all you need. If the whole thing, if you're too close to the blister, the real worry is that you will, in the processing of the tissue, the epithelium will come off, right? If the antibodies are there and they, we know the antibodies disrupt and so then you shake it around and you wash the Michelle's media off and all that good stuff. Like there's a chance that you will just that agitation and will, the epithelium will come off. Once that happens, you just can't, whatever you see, you can call it, but you're always like, mm, it might not be real. Um, legional skin is known to give false negatives, false positives, whatever. So you just really need something intact, some intact basement memories, don't be able to call it. So I'm not afraid to go right next to a blister. Okay. Marry and do do. Do all come or you never got to all do all do all commercial labs now offer, uh, BP 180 and BP 230. Is that pretty much, you know, your local hospital can, can get that? Well, I wouldn't say not all labs, but certainly many of the commercial labs and like if your hospital would then probably send off or to a reference lab, um, I think the real risk is that you could miss, I, I really love indirect immunofluorescence. And we're like, well, what's the big difference there? If you're only asking about BP 180, BP 230, you could miss inflammatory EBA, you know, you could miss, there's this new variant described P 200, Pempagoid is it, you know, clinically, it could look the same, but it could be negative if you're just doing BP 180, BP 230. So I think the benefit of doing an indirect is that you're going to see, there's antibodies at the basement membrane zone. If you're doing on salt split skin, you're going to see if they look like so that the Liam, you know, or to the dermal side. Um, and so it gives you a little more information. I don't think it's wrong to do the ELISA, but if it comes back negative and you have a real suspicion that this is an autoimmune process, you have to then chase it down with additional testing. I know Tim, what do you think about that? Yeah, I completely agree. Um, I want to say even the ELISA for BP 180 isn't it specifically like the NC 16 A. So if it's another epitope that the antibody happens to be binding to causing disease, uh, that ELISA actually won't pick up that antibody because I think it's very specific to that epitope. So the indirect is just right. It's you're going to catch a broader sort of, uh, array of targets that those antibodies might be binding. Yeah, and we, you know, we sometimes even do, you know, sometimes the indirect from serum is not positive, but we'll sometimes even take blister fluid and do an indirect, um, blister fluid and the antibodies are there and you can see them. So that's like a little tip if, you know, if you have a patient with very few blisters and you get a negative indirect on serum, you can do that as well. How do you work? I mean, I don't even know how you would order an indirect immunofluorescence is that out you can like type that in as an order into your EMR if you're not at a university and send somebody off to like commercial labs have it. Yeah. Okay. So let's go to Dr. Colton. Yeah, they did. We got a drum in a business. I didn't know. Most of the reference labs will do it. And then in terms of like commercial labs, um, many of them will do it. And I will say, right, it's something you don't order very often. So you have to like dig around and find out what are you actually ordering when you order these antibodies? Because they're all called different things and we all have different, you know, commercial labs available to us wherever we happen to be in the country. Yeah. So I think for Quest, you know, Quest is pretty popular. And sometimes what I, you know, what I also do, that's what, yeah, and that's what it's called. That's some of the other labs that we use as well. Um, but then some of them is like a package like you can order your Aliza and it's all the things, you know, is BP one, um, 180 BP 230 collagen set was like all the things you can order it. And it's like, comes all together. I'm sure there's still things we could be missing. So I always go back to DIF like you need that DIF. Um, that's going to be your most, um, sensitive.
So the average person who's in, you know, not like sitting down the hall from you, if they are in epic and they're putting an order in the computer or in your EMR, you can order anti-epidermal antibodies. You can send that patient to the lab. They will draw their blood, they'll process the serum, they'll send it to the reference lab. And in theory, you'll get that indirect IF. Maybe, I mean, I think it's called something different in every institution. Because like at our institution, it's indirect immunofluorescence is what you're putting in. If you want the ELISA, then that gets sent out to a reference lab. So I don't know what it's called at, at you guys places. Right, or most importantly, what's it called in modernizing medicine? Yeah. But you know, you ask, whatever you ask. And you say, this is what I'm trying to get. What is this? And I think mostly it's important just to know that they're different, right? Because you order something and then you get a result. And if you don't know exactly what you ordered or where the potential pitfalls are, you could miss something. So when somebody sends you an indirect IF, are you like, let me try to figure out, because you know, you memorize all these things for the boars, there's rap, bladder, there's monkey esophagus, there's this. Like, are you, is your kind of default? Like, I'm just doing this on salt split human skin or what's your default? Yeah. So, sadly, for direct immunofluorescence, your differential doesn't matter. If you ask me to do any of the IF labs, you ask to do a direct immunofluorescence, we're doing the same stains on every direct that comes in. Indirect's different. So it matters. If you tell me, I think this is pempagoid, then we're going to do it on salt split skin. And I won't do it on monkey esophagus. Unless that comes back negative, you're like, well, maybe it could be pempagus. But that's really, I think that's actually where the DIF helps us. Because if you do the DI first and you see the staining pattern there, then you kind of know what substrate to run the serum on. So that can be super helpful. But yeah, I think there's times where some new resident is thinking all their best thoughts about all the blistering disorders they ever knew or learned. And they put every single one on the requisition. And then we're testing it on all the different substrates with all the different secondary antibodies, right? Because you get the linear IgA disease is going to be different. You have to check with the secondary antibody against IgA. So it creates a lot of testing and a lot of bills if you don't put exactly what you think is going on. I really do think the direct can help you with that. So a lot of people order indirect trying to avoid having to do a biopsy for direct. But I don't think that's the best approach. So let's get back to some things that are probably a little more relevant to most of our listeners. So we talked a little bit earlier about the dipeptidial peptidase induced Pemphagoid. In your experience, what's kind of how long is somebody on the dipeptidial peptidase? Or could it be anywhere from a month to five years or is it usually a pretty long time? Or what's your take on it? I think it's a shorter latency period like Tim alluded to. I think it's like more like one to six months after you start those drugs that you would see it. And I will say, though, again, I totally read everything that was said, like we treat those patients like they have Pemphagoid. We try to, you know, get them to stop with their primary care versus prescribing it, get them to stop the culprit drug. And then we begin to taper just like we would if they're controlled on disease, we'd be in a taper, their treatment. And those are people who a lot of times you taper all the way off pretty quickly with no issues and life is good. And they sail off into the sunset and you think, I guess that looked and really did. That was the problem for them. Whereas the checkpoint inhibitor is like you said, much longer latency. And the way that the mechanism of action of a checkpoint inhibitor is like once you have like you said, let that journey out of the bottle, you cannot put it back for a lot of patients. So a lot of those patients will have just now they have Pemphagoid because you said it free. And it's really, I think it's really hard to control them by just like stopping the treatment and hoping they get better. You definitely have to treat them. And even then it's a lot of times longer term treatment like class. Okay. Do what is your, do you give every patient a topical steroid? I try. I don't think. Yeah. I like it. And you know, sometimes initially there's so much body surface area and they're looking at you with these big tense blisters like you want me to rub the cream all over these spots and I'm going to be all slicked up and not want to sit on my couch. And so, but yes, I do. And I say it's, you know, it's for your worst spots sometimes or especially as they're doing better and they just have a few overcalcedron areas left. And I like that's when we really lean in on the topical steroids. But no, I don't give club a dissolve from head to toe at the outset. Yeah. You don't do the, you don't do the phone. Shred your mom. I do not. I do not. Okay. Fair. Let's see. Anything else that we really want to, so it sounds like the big takeaway. If you, I'm going to ask you for a number. If you had to give me for quote, run of the mill, Pemphagoid. You know, just run of the mill. How frequently, how many people do you think Dupy is going to work in? I'm going to add my own caveats is that like if I can use prednisone and topical steroids and take however long I want to taper my prednisone, then I think it's probably going to be between 16 and 80%. Okay. Dr. Patten, what do you think? I was going to go like 50%. Like, yeah, what, what do I want to say? So you're on the prednisone and you start to do be and then you taper and you get off steroids and they're only on Dupy and that's preventing the relapses that's preventing having to do any sort of additional rescue therapy. I'm saying like half the time Dupy is going to be the answer. And that's what I like that's where it'll be the interesting. So I mean 60 to 80, it could totally be that number. I honestly have no idea. In the trial, where topical steroids allowed at all or no, nothing. Nothing. I considered rescue. They called. Yeah, I think they called that rescue therapy. Okay. And so maybe whenever we put Dupy together with a little bit of doxy and nice and a mind, it'll work a little bit better. Who knows? It's kind of one of the big takeaways. It's all right. Think about like, I don't know, I think back to like psoriasis and you know, I know in trials, you couldn't use it. But like, yeah, if I have somebody who can treat themselves with club azole three times a week and get one or two stubborn plaques done, like I'm happy with that outcome. I don't consider that a treatment failure. That's what I think is so hard here. And like one blister, one blister that needed a club azole and it was a failure. Yeah. We know, we know as dermatologists, we're pretty scrappy and we're going to mix and match and we're going to, you know, we're going to use all our tools. And so I think in real life, we're going to have a lot more flexibility and how we use everything and then how it works. We're going to see better outcomes. Yeah, because if you're, if they're on the Dupy and they flare and you're like, well, I'm going to put you back on 10. I think in the real world, we're not going to be like, I do pee is not working. Let's just stop it. It's not doing anything. Like we're going to say, okay, but if you weren't on the Dupy, maybe it would be 30 milligrams that we'd have to keep you on long term. So that's what I think we're going to figure out. I don't know. Don, did you think antibody, like, what do I want to say? Like the tighter spectrum, like some patients will respond better if they're 230s higher than they're 180. Maybe. I mean, I think that's where the fun for us will be is blistering people, right? We get to figure out, we call it like disease endotypes or, you know, who's going to respond to what and who's really more of like a type two inflammation and Dupy will be great for them and other people who maybe that's not really what is driving their disease. So I do think there's going to be some fun to be had and figuring out who Dupy works for and who it doesn't. Yeah. Okay. Well, let's jump over to our patent unless patent fairs, you guys got anything else before we jump over to our patented patent trivia. I was so engaged in this conversation. I had no idea what you were kicking it over to. I totally forgot about my trivia. Sounds right. Which usually this is the only thing I look forward to on the show. All right. So it is blisters. It's blister, blister trivia. Okay. Okay. We're ready? Yep. All right. What song is the first track of the 1983 self titled debut album by the violent. Blister in the sun. Yeah. Blister in the sun. On the board. In my mind, I was thinking it's got to have a violent films question and it's a blister. So I was ready. It's already strategizing. Exactly. Yeah. Very good. All right. I'm keeping with the music theme. I go away from music theme. Third question. And it's actually more medically related. So hang in there if you don't like music. Ringo star. Shouts out the phrase. I got blisters on my fingers at the very end of what Beatles tracked from the white album. No idea. I got nothing. Okay. Any track from the white album. I don't want to throw out a guess. I would go. I'm in. So let's see only one like. Yeah. Different album. It was a music.
Thank you, Shigmef. Thanks for participating. The song was "Helter Skelter." Oh, okay. Okay. Helter Skelter, all right. Yeah, classic little bit of Beatles trivia there. All right, number three. "Auro contraceptive medications were the first types of medications to be distributed in what type of packaging?" "Listerpacks." I think was that it probably got three way ply. We all got that. I got Matt first, but I think with delays and Matt, you're closer to I than to me than it's true. You and see people, so I think it's a top. I heard a lot of firsts, so there you go. That's the geography. It's true. It's true. That's true. All right, so I'm calling it a tie, so that's pharises with the. One. "Lister in the Sun." All right. Good work, pharise. Thank you. All right. All right. We want to thank our listeners for joining in this this week. If you've got questions, comments, ideas for topics, for cover on the show, shoot a snail at
[email protected]. We hope you learned a few things. We have to laugh once you're twice, and mostly we're hoping you're planning to join this next week. Until then, I'm Matt Cyrus. I'm Tim Patton. And I'm Laura Ferris, and we are Derms on drugs.
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