Audio file
Reid Final.mp3
Transcript
00:00:00 Jenn Dawson
Hello and welcome to PeDRA Pearls, the podcast from the Pediatric Dermatology Research Alliance.
00:00:06 Jenn Dawson
We are a vibrant research community pursuing a mission to create, inspire, and sustain research to prevent, treat, and cure childhood skin disease.
00:00:16 Jenn Dawson
Each week, we bring you inspiring stories, research updates, and practical information to advance science that improves the lives of children with skin diseases and conditions.
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I'm Jenn Dawson, host of PeDRA Pearls and PeDRA’s Director of Educational Programs.
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I'm so glad you're here.
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In this episode, I sit down with Dr.
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Reid Oldenburg for an in-depth conversation about his path into dermatology, his passion for translational research, and his leadership of PeDRA’s Drugs and Bugs focused study group.
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Dr.
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Oldenburg shares how early experiences, from field research on rare infectious diseases in West Africa to complex immunology lab work, shaped his clinician-scientist career.
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Together, we explore the origins and purpose of the Drugs and Bugs Focus Study Group, the importance of clearly defining conditions like RIME and SJS and TEN,
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and the major ongoing research efforts aimed at improving diagnosis, treatment, and patient support for severe cutaneous adverse reactions.
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So let's jump in.
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Welcome to PeDRA Pearls, Dr.
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Oldenburg.
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I am so excited to be speaking with you today.
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So let's start with a little bit of background about you.
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Tell me about your journey into dermatology and research.
00:01:43 Reid Oldenburg
Yeah, thanks.
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Yeah, thanks so much for having me.
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It's so cool to finally be here.
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And I'm so glad that I've had a chance to work on some of the projects and report back to you.
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So yeah, thanks again.
00:01:53 Reid Oldenburg
I'm Reed Oldenburg.
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I'm an MD-PhD, so I'm a clinician scientist.
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And I work at UC San Diego, the VA, and at Rady Hospitals.
00:02:01 Reid Oldenburg
My breakdown currently is I do about 40% of my time in the clinic.
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And then I've always really liked research.
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So I'm spending as much time as I can in the lab and doing about 60%
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percent of my time doing research.
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And a lot of the research has been very translational because I've been focused just on getting high-quality patient samples, understanding the inflammation and the immunology and the immunopathomechanisms of disease in these patients.
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And so yeah, I really do, I'm kind of a jack of all trades right now, but I really do, the biggest focus of my work is in the translational science
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space.
00:02:40 Jenn Dawson
And was research always the career goal for you, or is that something you discovered a passion for at some point in your training?
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Can you talk a little bit more about that?
00:02:50 Reid Oldenburg
Yeah, I definitely always knew that I wanted to do basic science research, and I wasn't sure.
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Sure, exactly.
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In the beginning, if I wanted to do medicine, but once I got into research, I was working in a couple different labs as a research assistant.
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And once I started to be in the lab, I realized how much I wanted to work with people and actually see patients.
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And I really felt like the most interesting research really comes from things that are happening in real people because patients obviously with an inflammatory disease, there's so much to be understood about the particular patient, but then there's a huge thing that there's just so much to understand about the disease in general.
00:03:27 Reid Oldenburg
And with all of the new science that we have, we have new techniques that can understand disease processes, but then we also have new drugs that are being marketed and approved so that we can combine techniques with medications to really make
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make patients' lives better.
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And I think my personal journey really started with, I was doing a summer internship at the Pasteur Institute in Paris.
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And I got involved in a project that to me was very translational, where we actually, I was sent in the field in West Africa and Ghana to study a rare dermatologic infectious disease called Buruli ulcer that is caused by an actual mycobacteria.
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And I just felt like it was so fun to be there in person, meeting the
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patients.
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And it was such an understudied disease at the time that it was just, to me, it was so exciting to actually talk to patients, go visit the towns where maybe they were getting infected with the pathogen, and then actually you collect samples from the patients, get clinical data from them.
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So I felt like it was a very alive research project that made me really enjoy the whole process.
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And it was so social, it was so fun.
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So that was really, I think, my initial introduction to translational research.
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And then during that project in the lab, I was offered a PhD spot to continue research in mycobacterial infections.
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So mycobacteria cause, you know, Hans' disease or formerly known as leprosy, they cause tuberculosis.
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And then I ended up doing a very rigorous or more strict PhD in understanding the host pathogen interactions of how mycobacteria, how they alter immune function and how they infect people in the 1st place.
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So it was like, it went from really the patient-centered thing into the lab.
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So I followed that trajectory, which is pretty much how I started in the world of research.
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When it comes to drugs and bugs and the work that I've been now lucky enough to have been a part
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or be a part of PeDRA and work on.
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When it comes to drugs and bugs, it really started once again with the patient again, where I was a dermatology resident and I started seeing patients with reactive infectious mucocutaneous eruptions or RIME.
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Being an immunologist or being a sort of,
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aspiring immunologist, I kept wondering, what is actually going on in these patients?
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what actually causes the blistering?
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And after talking with, my mentors like, Larry Eichenfield, I started to learn that there were so many more questions.
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And that's how I ended up meeting folks in PeDRA and how I really found a way into my current lab and current research setup where I work.
00:06:02 Jenn Dawson
Oh my goodness.
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Thank you so much for sharing that background into what inspired you to be both in the lab and working with patients.
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This is just really cool.
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I had no idea about your story and your trip to Africa.
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That sounds amazing.
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So there's a lot that I want to go in on here.
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But let's first, let's kind of focus on the drugs and bugs piece, because you did mention drugs and bugs.
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And that is what we call a research focused study group here at PeDRA.
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For those listeners who are unfamiliar, PeDRA sort of brackets their research in these different buckets of disease focused area.
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So drugs and bugs is one of our newer
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of study groups.
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So if you could just give our listeners like a quick definition of what that group is.
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I know you mentioned rhyme, but let's kind of dive into what that group is and then we can talk about what it does.
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Right, so in my understanding of the history of drugs and bugs, because it predates me, is that it really was related in the beginning to understanding some of the severe cutaneous adverse reactions and really focused on pediatric dermatology patients.
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So drugs and bugs, I think, started off early with just trying to define some of the terms.
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And I think the term
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RIME, or Reactive Infectious Myocoputaneous Eruption, essentially was in the early stages of the FSG before it really formally existed.
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And so essentially, drugs and bugs was designed to answer everything that is drugs and bugs.
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So of course, the major focus would be the scary things in pediatric dermatology, which are the severe cutaneous adverse reaction.
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So pediatric dermatology, you know, having fewer expert clinicians in the community and then having
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less research previously in the adult world.
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I think for the FSG, it was really dedicated to bringing together the brightest minds in North America and internationally and really studying everything that is drugs and bugs.
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But of course, historically, it has been more focused on the pathogen-triggered mucocutaneous eruptions like Ryme and then, of course, Steven-Johnson syndrome, toxic epidermal necrolysis,
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in some of these really rare and severe diseases.
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But in reality, drugs and bugs would cover anything that is drugs or bugs.
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So of course, there have been other projects on tinea or ringworm.
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There have been projects on medications and other allergies.
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So it really is a wide basket.
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And now, one of the other medications that, of course, our group is now studying are JAK inhibitors and how that affects people.
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So really, it's a very broad
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FSG that covers a lot of different topics, but historically, and I think our current projects really are majorly focused on the severe cutaneous adverse reactions.
00:08:53 Jenn Dawson
And what was it about severe cutaneous adverse reactions that really attracted you and that you wanted to learn more about?
00:09:00 Reid Oldenburg
I think that by definition, they're severe and they're very terrible.
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So I think when you're, as a dermatologist, you know, these are some of the scariest things that we see in clinic.
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or in the hospital.
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And these are patients that are really suffering A lot.
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So I think just for immediately, of course, in training and then in the early years after training, it's a very easy thing to want to help patients with because the patients present so dramatically, they're so sick.
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And then there's also so many major questions in understanding these diseases, both clinically and from a basic science perspective, that it makes it in a lot of ways, it makes it very easy to be attracted to because it's like, there's so much potential to help people essentially.
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Yeah, I can definitely see why you and your colleagues who are studying these severe cutaneous adverse reactions are so passionate about it.
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And now you are leading the charge as the chair of this group.
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So give me some details and some insider information into what the group is working on, what projects are upcoming, if you need any collaborators.
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I just want to know what's going on in the group.
00:10:07 Reid Oldenburg
Right, and there's a lot of ongoing projects and it's always a challenge because everyone has their full clinical schedule to work with.
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So our projects are have a little bit of a, they have, it's like a, it's almost like a dinosaur walking, like it takes time to make progress, but we are moving.
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We have momentum and everything, you know, happens in time.
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And we have a lot of ongoing projects.
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In terms of discussing ways to help, I'm going to share with you a,
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an electronic system that we have where we can actually track different projects.
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So I'll share that with you and you can put the link in the bio as well, because we're looking for ways to match people and we have chat rooms and we have ways that we can set deadlines.
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So I'll definitely share that with you.
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The group is, there's a major focus, of course, as in PeDRA, to really bring together the minds that we have and develop consensus, and it can be consensus via, can we come up with consensus guidelines to better treat, to diagnose?
00:11:10 Reid Oldenburg
And of course, historically, this FSG has really been dedicated to Rhyme because that's where a lot of major questions still exist.
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So the group at large, the FSG, many of the individual members of our group are working on developing consensus guidelines.
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So one ongoing
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publication will be dedicated to just bringing clinicians together and providing a nice roadmap for those that are maybe less expert and those that are residents that are trying to learn more about rhyme and to revise the diagnostic criteria.
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So there's definitely a focus to improve our
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our outward communication on what rhyme is.
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And then there is an ongoing consensus, really bringing the actual, the best minds of rhyme together and then identifying good treatment algorithms.
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So I think that's a really nice upcoming publication that I would anticipate we would be seeing in the next one to two years.
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And I think that will be really helpful because really, it's, I think it's really interesting talking to, you know, the great minds of rhyme, like, you know, Yvonne Chu and Michelle Ramin,
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There are so many things that are very intuitive to them because they have a high volume of patients that they take care of.
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And what we really want to do is we want to try and transmit some of these key knowledge points between the key opinion leaders and give it to the public so that the, or just residents and maybe younger faculty members, so that they can take this and understand some of these intuitive points and operationalize them and actually say, okay, how do I measure this?
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How do I understand if a patient's progressing?
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How do I decide to go up with therapy?
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So I think those
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That's going to be a major, I think, one of our capstone projects in the next one to two years that I'm very excited about.
00:12:51 Jenn Dawson
Well, those two projects in and of themselves sound like a massive undertaking and something that this space really, really needs, especially when you're talking about educating other providers who are going to be seeing this
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in their ERs or in their clinical practice.
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What else is going on in the group?
00:13:09 Reid Oldenburg
So one of the projects that we have that's ongoing, that I'm not directly involved in, that I'm very excited about, is Yvonne Chu, Michelle Romine, and Beth Rolle.
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I think it was back in 2020, they launched a project
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to study Ryme patients and then do genetic sequencing of them and their parents.
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So the idea here is really to look for genetic susceptibility markers because maybe there's something in their actual genetic, in the patient's actual genetic makeup that.
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results in them developing Ryme.
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Maybe, for example, when they encounter a certain pathogen, like mycoplasma pneumonia is a very common trigger for Ryme.
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Maybe when they encounter that, there's something in their genetic makeup, whether it be something like a cytokine or a protein recognition molecule that causes them to develop these things.
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So I'm very looking forward to, they have a large team of collaborators that I can't name them all, but they have folks that are doing their informatics.
00:14:04 Reid Oldenburg
And I'm looking forward to understanding to see if, is there a genetic marker that can help us predict Ryme?
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But I think also it's going to be really interesting to put these genetic markers into the context of inflammation and understand, you know, maybe it's going to help us really understand what inflammatory pathways are dysregulating in these patients as well.
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So that's a really fun project that I'm looking forward to seeing results for.
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We also have a lot of other clinical research projects.
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So
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Harper Price is doing work on survey work and just getting, once again, bringing our FSG talent together and understanding what some of the barriers, diagnostic needs are, treatment and management needs are for pediatric Stephen Johnson's or toxic epidermal necrolysis.
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So SGS and TEN, for those of our listeners that are not as familiar with these terms, these are drug-triggered severe cutaneous adverse reactions that do resemble
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rhyme.
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And so the drug-triggered ones will cause blistering of the mucous membranes and the skin and can be very life-threatening and very scary, and they're triggered by medications.
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But what's really important for us to evaluate from a clinical perspective, especially in pediatric patients, is how are providers using different therapies to treat the immune system?
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And then how are we doing the basics, like wound care?
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And
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of the room temperature.
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How are we actually, so really these minor details, because really the importance is really in this detailed multidisciplinary care.
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So Harper Price is going to bring together some ideas from all over our community to really understand how these differences exist in different centers so that we can learn from each other.
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So that's another really interesting clinical project.
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I definitely also want to highlight the work from Fiona Lynch, who is one of our liaisons
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who we're hoping to bring into the leadership of this FSG in the future, if she's able to, because she may be recruited somewhere else.
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But if she's able to, we would love to recruit her.
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And she's done a lot of work in terms of community engagement.
00:16:10 Reid Oldenburg
So, you know, reactive infectious mucocutaneous eruptions,
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They're essentially, these pathogen triggered.
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So people get walking pneumonia.
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And then about a week later, they develop these horrible blisters of their mouth and eyes and can get hospitalized for, you know, for weeks at a time because they're unable to even eat.
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And this affects, you know, children and it can happen over and over again.
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So some patients will get it, you know, once a year or multiple times.
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And it's extremely disruptive for patients.
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they lose a lot of weight, they can't do sports, and it's a terrible disease.
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So one thing that Fiona is doing is she's working to develop patient-centered resources.
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So how do we have a patient-centered resource?
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You know, how do we describe what rhyme is for folks that are affected by rhyme?
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How do we put it into terminology that is easy to understand for, you know, a lot of our patients are 12, 13, 14 years old.
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So
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We're going to work, and Fiona's doing some excellent work to understand, different ways of conveying information to different age groups.
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So I'm looking forward to see some of those patient-facing resources because we currently have a lack of those.
00:17:19 Reid Oldenburg
She's also coordinating with Yvonne Chu and Michelle Romine to help find patients for the genetic study.
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And then she is doing retrospective studies, which basically means look at all the patients that had rhyme at
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a center and then look back at how they did, what were the triggers, what was the treatment that was used, how did the patients actually do?
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So she's putting together a really nice study looking back through records at her hospital and I'm looking forward to seeing a publication from her soon.
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She has the manuscript is currently in writing there.
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So I think, you know, she's been such a fun member of our group that's been very dynamic, so we're lucky to have her input as well.
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And then
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We're also, another thing we're doing is we're coordinating with another, and this is one thing that we're always trying to do is talk to our, how do we talk to our FSG colleagues, you know, because we have all these other FSG, and there's a lot of overlapping interests.
00:18:14 Reid Oldenburg
And one of the recent overlapping interests that we have is JAK inhibitors are now, of course, these are systemic small molecule inhibitors that are being used to
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inhibit inflammation that is, and these medications are really helping patients who have atopic dermatitis or really bad eczema, and it's also helping one of our non-scarring hair loss disorders, alopecia areata.
00:18:36 Reid Oldenburg
So a lot of different patients in varying age groups are now on JAK inhibitors.
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And we're working with an ongoing study to understand and see if JAK inhibitors are affecting certain patient outcomes, particularly their growth and how they're doing overall.
00:18:52 Reid Oldenburg
Because of course, JAK inhibitors are a newer medication.
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And so we're doing a lot of work with others to improve the pharmacovigilance of these medications.
00:19:02 Jenn Dawson
Oh my gosh, that is a lot happening in this focus study group.
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I am thrilled to see so much wonderful work coming together, especially
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that piece about developing content that's appropriate for different age levels of patients.
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That is so important.
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So that's a pretty comprehensive overview of what the group is doing.
00:19:22 Jenn Dawson
And if it's okay with you, I just want to pause here on the research portion because some information just finally gelled for me about the work that Drugs and Bugs is actually doing.
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And I just want to go off on a little bit of a tangent here.
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So bear with me and listeners, I promise it'll be worth it.
00:19:39 Jenn Dawson
Way back almost three years ago in 2023, I recorded a podcast with Dr.
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Michelle Ramin, Dr.
00:19:47 Jenn Dawson
Erin Mathis, and Dr.
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Yvonne Chu, where we were really talking about the differences between rhyme, SJS, and TEN, and really kind of why the naming of these
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conditions matters.
00:20:04 Jenn Dawson
And you really helped crystallize for me that, rhyme is triggered by a pathogen where SJSTEN is triggered by medication or a treatment.
00:20:14 Jenn Dawson
That's not something that I think was really clear in my head, but now it is.
00:20:19 Jenn Dawson
So I want to talk to you a little bit about like how have we evolved since just 2023 when we were talking about this sort of being a jumbled up mess and why is
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is it important to have these specific definitions for these conditions?
00:20:37 Reid Oldenburg
Oh yeah, completely.
00:20:38 Reid Oldenburg
And I think this is where, the naming of diseases and identifying things is so important.
00:20:44 Reid Oldenburg
And if I was this discussion in medicine about lumpers and splitters, the reason, I think that the philosophical reason for splitting and for actually breaking down these diagnoses is because if the trigger, if the cause is different, then the actual
00:21:02 Reid Oldenburg
the actual inflammation and the actual problem that the patient is facing could be also different.
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So just because things look similar does not actually mean that the trigger is the same exact thing.
00:21:14 Reid Oldenburg
And so it's actually pretty interesting because some patients with really bad, when they have really bad flares of lupus,
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their reaction can actually have some overlapping features with what we see in Rime or SGS and TN.
00:21:28 Reid Oldenburg
So I really do think that, of course, you know, you do have to be careful with creating all these different names because you don't want to confuse the audience and you don't want to confuse, you know, you don't want to confuse people who may not see these diagnoses frequently.
00:21:40 Reid Oldenburg
I agree with the work done by other FSG members in that you really want to understand
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what is the trigger so that we can actually direct a workup to properly diagnose the patients.
00:21:52 Reid Oldenburg
And then you do want to be able to have a clear diagnosis of pathogen triggered versus drug triggered because now we're starting to see that the pathogen triggered or RIME cases, the RIME cases actually have a different clinical course.
00:22:06 Reid Oldenburg
They tend to have less skin involvement.
00:22:10 Reid Oldenburg
they tend to more be younger and have more eye involvement.
00:22:14 Reid Oldenburg
And then they also, you want to have the appropriate diagnosis and understand rhyme because then you're going to look for that pathogen trigger, which in the case of mycoplasma, you can.
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direct antimicrobial therapy to treat that.
00:22:26 Reid Oldenburg
And a lot of patients, will have actual, they'll have chest x-ray findings or they do have signs of atypical pneumonia.
00:22:32 Reid Oldenburg
So I really do agree with the work done by former, you know, by former really important publications about actually splitting this.
00:22:40 Reid Oldenburg
And I think this is where we're lucky to have a community like PeDRA because by bringing our resources together, we're able to have publications with consensus that means that these diagnostic terms will actually get
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out of North America and we'll get to the rest of the world.
00:22:55 Reid Oldenburg
Because when you explain pathogen triggered, rhyme to people in other countries, they may not know that term.
00:23:02 Reid Oldenburg
So sometimes you actually have to say pathogen triggered SGSTN.
00:23:05 Reid Oldenburg
And so your confusion around the idea, and it's actually very, it's not even really a confusion.
00:23:12 Reid Oldenburg
It's more just we don't have consistency, you know, internationally in terms of
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of what the nomenclature really is.
00:23:19 Reid Oldenburg
And so I think, just by repeating these publications, it's really valuable.
00:23:23 Reid Oldenburg
But I think even just putting a name rhyme on this, it was so valuable because it allows, funding agencies like the NIH and it allows for more directed research to understand some of these questions.
00:23:37 Reid Oldenburg
And so the mechanism that why does mycoplasma pneumonia, why does it cause mucocutaneous eruptions?
00:23:43 Reid Oldenburg
The mechanism has been
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unknown.
00:23:46 Reid Oldenburg
And the first cases of this have been described over 100 years ago.
00:23:50 Reid Oldenburg
So it just really goes to show that when you name something and you start to split it and really have a clear diagnostic term, it really helps.
00:24:00 Reid Oldenburg
And of course, the obvious thing is that when you have a clear diagnostic term, it allows you to study
00:24:07 Reid Oldenburg
individualized and molecular based therapies for that specific thing.
00:24:12 Reid Oldenburg
Because as a patient, you don't want to be the one-size-fits-all.
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Everyone is special and you want the treatment that works for you.
00:24:18 Reid Oldenburg
So of course, by having more individualized diagnostic and more precision in our diagnosis, it allows you to have a more precise treatment as well.
00:24:27 Jenn Dawson
That was so helpful.
00:24:29 Jenn Dawson
Thank you for allowing me that tangent.
00:24:33 Jenn Dawson
But it really illustrates why this work is so important.
00:24:36 Jenn Dawson
So let's use this time to shift into our conversation about some of the projects that you yourself are specifically working on.
00:24:43 Jenn Dawson
So I know you and several others all worked together on a recent publication that appeared in JCI Insight back in November that was supported by a 2020 PDA research grant.
00:24:56 Jenn Dawson
And the title of that project was Dual Dysregulation of TNF-IFN,
00:25:01 Jenn Dawson
signaling, and classical monocytes are implicated in reactive infectious mucocutaneous eruptions.
00:25:09 Jenn Dawson
And then you also published an abstract at the PDRA 2024 conference titled Deciphering the Immunopathogenesis of Reactive Infectious Mucocutaneous Euption.
00:25:22 Jenn Dawson
So talk a little bit more about those projects, possibly how they're linked, and what you're learning.
00:25:28 Reid Oldenburg
Right, and the thanks for, thanks for offering the opportunity to talk about this research, because of course it's very exciting and I think it's a really exciting time and it's really a good continuation on this idea of now that we have this diagnostic term, how do we, how can we break it apart and how can we actually understand the path of mechanisms of what is actually happening in these patients?
00:25:49 Reid Oldenburg
And the two projects are really linked because they're really just one long continuous journey.
00:25:56 Reid Oldenburg
And as our research listeners know, it's such a journey.
00:25:59 Reid Oldenburg
These projects always take longer.
00:26:02 Reid Oldenburg
Yeah, and essentially it's collaborative in a sense where we have been working collectively with our entire pediatric dermatology faculty here at Rady Children's Hospital, and we've been working with all the residents and have been working with two different basic science labs
00:26:19 Reid Oldenburg
and have also worked with collaborators that do bioinformatics at the La Jolla Institute for Immunology.
00:26:26 Reid Oldenburg
So we have a pretty large group of people.
00:26:28 Reid Oldenburg
And essentially what we're doing is we're collecting samples from active Rime patients.
00:26:34 Reid Oldenburg
So when they actually are experiencing the inflammatory effects of Rime, and we are taking their samples, we're taking their blood, and when we can, if it's possible, we get blister fluid from the patients.
00:26:47 Reid Oldenburg
And then what we do is we
00:26:49 Reid Oldenburg
we do what we call single cell RNA sequencing, which essentially means we take each individual cell from their blood or from their blister fluid, and we put them into little microchips essentially, and then we sequence all of the RNA, meaning the gene signature in each individual cell.
00:27:07 Reid Oldenburg
And even with like 10,000 or 15,000 cells, you can get an unbelievable amount of information because now what you're doing is you're looking at
00:27:17 Reid Oldenburg
not just all immune cells.
00:27:19 Reid Oldenburg
You're looking at the monocytes, the T cells, the B cells.
00:27:22 Reid Oldenburg
And then you can see what inflammatory pathways are upregulated in the patients.
00:27:28 Reid Oldenburg
And it's very difficult research.
00:27:29 Reid Oldenburg
So essentially, the biggest challenge is actually getting the patients, finding the patients in the emergency department early on.
00:27:37 Reid Oldenburg
and then also finding them when they've recovered.
00:27:40 Reid Oldenburg
Because what we do is we get their sample while they're having active Ryme, and then we find them, usually three months, six months later, and then we ask them for another sample so that we can compare their inflammation to when they're recovered.
00:27:55 Reid Oldenburg
And this has been really valuable.
00:27:57 Reid Oldenburg
And our first, you know, our first publication
00:28:00 Reid Oldenburg
on this was a group of all comers with Ryme.
00:28:04 Reid Oldenburg
So we found any patient that had Ryme, and then what we did is we took their serum and we sent it for cytokine analysis, and we looked at almost, I think it was 300 different cytokines.
00:28:14 Reid Oldenburg
and we identified to see if there was an overlapping, inflammatory signature.
00:28:20 Reid Oldenburg
So like, you have five different RIME patients.
00:28:22 Reid Oldenburg
Are they similar?
00:28:23 Reid Oldenburg
Do they have the same inflammatory signaling?
00:28:25 Reid Oldenburg
Because maybe they have different triggers.
00:28:27 Reid Oldenburg
Maybe one had, you know, COVID was a trigger, one had adenovirus as a trigger, another one had mycoplasma.
00:28:32 Reid Oldenburg
And it's really interesting to actually look at this diverse group of patients with different triggers and see if there's actual overlapping inflammatory signaling.
00:28:42 Reid Oldenburg
And this first initial report that we published
00:28:44 Reid Oldenburg
published, I think it was just two months ago now, was able to identify that there is a signature that we think links dysregulation of TNF, which is an important cytokine, and then also interferon signatures.
00:29:01 Reid Oldenburg
So the TNF piece is very validating and important because currently one of the
00:29:09 Reid Oldenburg
more accepted therapies for Ryme is a tannerceptor, which actually inhibits TNF-alpha.
00:29:17 Reid Oldenburg
So that TNF is an inflammatory cytokine.
00:29:21 Reid Oldenburg
And we know, extrapolating from the literature from SGS and TN from the drug-induced ones, we know that TNF is probably contributing to cell death, which is the, you know, of course, the mucous membranes and the skin.
00:29:32 Reid Oldenburg
And so we were able to validate that in this small series that there's dysregulation in these two things.
00:29:39 Reid Oldenburg
It's definitely a nice step, but I really think we have a ton more work to do.
00:29:44 Reid Oldenburg
the upcoming project now that we're doing is we've been collecting samples just of patients with mycoplasma pneumonia-triggered RIME.
00:29:53 Reid Oldenburg
And the reason why we want to do that is because we really want to try and collect a very consolidated group of patients so that we can
00:30:01 Reid Oldenburg
we can further dig and do more of the transcriptomics.
00:30:04 Reid Oldenburg
And so I'm very happy that PeDRA actually is supporting the next phase of this research.
00:30:11 Reid Oldenburg
So I'm very lucky.
00:30:11 Reid Oldenburg
And I just want to thank PeDRA, of course, for funding the next grant, which will actually continue to do this work in these patient samples.
00:30:21 Reid Oldenburg
Because now, of course, it's been four or five years since I've been collecting these samples.
00:30:24 Reid Oldenburg
So now we have more samples that we can analyze.
00:30:27 Jenn Dawson
I'm wondering if you could comment or talk a little bit about the value of bringing in other specialties when you're working on projects like this.
00:30:35 Jenn Dawson
Like you mentioned, you're working with people in immunology.
00:30:38 Jenn Dawson
I see that Bob Gang is on your publication.
00:30:43 Jenn Dawson
So why is it important to bring other specialties to the table?
00:30:49 Reid Oldenburg
It's the potential of working
00:30:52 Reid Oldenburg
interdisciplinary is really endless.
00:30:54 Reid Oldenburg
And I think it comes from a lot of different angles.
00:30:56 Reid Oldenburg
I mean, first of all, bringing people from other specialties is valuable because they have had similar questions in their field.
00:31:04 Reid Oldenburg
So a good example is Hal Hoffman, who worked a lot with the periodic fever syndromes.
00:31:09 Reid Oldenburg
There were so many questions that he had to answer.
00:31:11 Reid Oldenburg
And so just talking to someone like him
00:31:14 Reid Oldenburg
or talking to someone, one of the Kawasaki disease experts and just saying, how did you start your work?
00:31:19 Reid Oldenburg
How did you break this down?
00:31:21 Reid Oldenburg
So there's just almost, you know, it's almost like an apprenticeship.
00:31:23 Reid Oldenburg
It's just asking, it's just asking people, well, how did you do it?
00:31:27 Reid Oldenburg
And I think just through experience, through learning from others, and then, you know, rheumatology, for example, they have all these inflammatory markers.
00:31:34 Reid Oldenburg
Bob Gang works in allergy and immunology.
00:31:37 Reid Oldenburg
So there's this whole other experience in, you know,
00:31:42 Reid Oldenburg
genes, inflammation, understanding rare diseases that comes from that.
00:31:47 Reid Oldenburg
So essentially by bringing together a large group of mentors and colleagues or whatever you want to call them, I'm able to get experience and learn from them directly from a pragmatic standpoint.
00:31:58 Reid Oldenburg
So how did you do this?
00:31:59 Reid Oldenburg
Oh, I did it this way.
00:32:01 Reid Oldenburg
You know, having an IRB, you talk to the IRB.
00:32:04 Reid Oldenburg
Then of course, you know, when it comes to some of the more nuts and bolts,
00:32:08 Reid Oldenburg
you mentioned collaboration.
00:32:09 Reid Oldenburg
So we have a key set of collaborators with bioinformatics.
00:32:13 Reid Oldenburg
And so obviously, I'm not capable of sitting and coding and doing all the codes.
00:32:20 Reid Oldenburg
So, the best thing that I can do is from my clinical perspective, I have this perspective that I can offer.
00:32:26 Reid Oldenburg
And the best thing that I'll do is I'll sit next to the bioinformatician and, you know, we'll just talk, you know, over the course of a day.
00:32:33 Reid Oldenburg
I'll look at the data and see what the inflammatory signaling is in real time, what the single cell RNA sequencing is showing.
00:32:41 Reid Oldenburg
And then when I look at the data, I'm able to, through experience and once again talking to this collaborative network, I'm able to pick out the inflammatory markers that have a story behind them and actually make sense in the context of the patient.
00:32:56 Reid Oldenburg
So the informatician is really
00:32:59 Reid Oldenburg
they're really able to dig deep, but then it comes to, then it comes to us and it comes to me in this meeting setting.
00:33:06 Reid Oldenburg
And then we're able to take everything in context and say, okay, well, what does this actually mean?
00:33:11 Reid Oldenburg
Does this mean that we can use a different therapy for this?
00:33:14 Reid Oldenburg
Can we analyze this?
00:33:15 Reid Oldenburg
Can we analyze that?
00:33:16 Reid Oldenburg
And it's really that back and forth that allows the work to go.
00:33:19 Reid Oldenburg
But I mean, to answer your question, I mean, it's really just, there's so much benefit that you get from working with people.
00:33:27 Reid Oldenburg
And having the right people that share the motivation is so critical.
00:33:31 Jenn Dawson
Yeah, I really like how you put it, especially when you said that their questions probably aren't so different from the questions you're asking too.
00:33:38 Jenn Dawson
And so you have this chance to really work together.
00:33:42 Jenn Dawson
And then everybody brings their box of puzzle pieces.
00:33:45 Jenn Dawson
And then with everybody there, you can start putting the puzzle together.
00:33:50 Reid Oldenburg
Yeah, absolutely.
00:33:50 Reid Oldenburg
and I definitely actually want to also give a shout out to Lori Broderick, who helped me contextualize things and understand inflammation and really break things down because she had a fantastic story looking at pansquotic morfare.
00:34:04 Reid Oldenburg
And it was very similar.
00:34:05 Reid Oldenburg
It was, you know, these diseases have been understudied and how do you break apart these available tools and how do you apply it to a problem?
00:34:13 Reid Oldenburg
So, yeah, I mean, completely, it's all about it's all about that persistence, but it's all about, you know, working together and then also
00:34:20 Reid Oldenburg
So, just communicating clearly with team members and just taking that time to just have patience.
00:34:27 Reid Oldenburg
everyone has a different skill set, so sometimes we almost need like a translator there to talk to each other, but we get through it, and it's really just the patience and the communication that brings everything together.
00:34:38 Jenn Dawson
Yeah, it sounds like just a really impressive group that you all have assembled and have going.
00:34:44 Jenn Dawson
And I know that your efforts will be rewarded, certainly.
00:34:48 Jenn Dawson
We are coming to the end of our interview, which I am not happy about because I feel like there's so much more we could talk about.
00:34:56 Jenn Dawson
But I just wanted to close with a few final questions.
00:35:02 Jenn Dawson
I want to think about the future.
00:35:05 Jenn Dawson
I want to think about the future of the Drugs and Bugs Group and of your career and your inspiration and your work in research and where you see all of that in the next five years.
00:35:20 Reid Oldenburg
Right, yeah, thanks for the question.
00:35:21 Reid Oldenburg
It's been such a fun discussion too so far.
00:35:23 Reid Oldenburg
You know, I think what will be really valuable for the FSG is really just continuing a lot of these projects.
00:35:30 Reid Oldenburg
And I think,
00:35:32 Reid Oldenburg
And I think we need to, with, and I won't be, I think next year I won't be president.
00:35:36 Reid Oldenburg
So I think the next leadership, we're really going to have to continue to work to bring in other topics outside of Rhyme, because we've really been focused on Rhyme and SGS.
00:35:46 Reid Oldenburg
And then also, I didn't really mention DRESS syndrome, but I think there's a lot of opportunities in the world of DRESS syndrome.
00:35:51 Reid Oldenburg
So I think, you know, the first thing we want to do is we want to continue the clinical work.
00:35:56 Reid Oldenburg
We want to build more consensus.
00:35:58 Reid Oldenburg
And then another thing that I think in Rhyme that we have in our early phases, and we're talking to different members, is we're going to need to develop an activity score.
00:36:09 Reid Oldenburg
Because for Rhyme, it's really hard to tell, and our expert clinicians certainly can, and we know they can, but it's very hard to tell for people with lower patient volume or residents, it's really hard to tell how active
00:36:22 Reid Oldenburg
the patient actually is like, are they getting worse?
00:36:24 Reid Oldenburg
Is there inflammation?
00:36:26 Reid Oldenburg
How do we know that a treatment is not working?
00:36:29 Reid Oldenburg
And so one thing I'm currently in early discussion with Yvonne Chu and Michelle Ramin is we're going to try and develop a clinical activity score for RIME.
00:36:38 Reid Oldenburg
And I think an activity score will be really good because it's different from severity because activity is going to really help us in real time understand what's happening with the patient.
00:36:47 Reid Oldenburg
How do we
00:36:48 Reid Oldenburg
How do we proceed with treatment?
00:36:49 Reid Oldenburg
So that's one thing I think is going to be valuable from the clinical perspective is an activity score.
00:36:54 Reid Oldenburg
And severity score is also important as well.
00:36:56 Reid Oldenburg
RIME does not have an ICD-10 code.
00:36:58 Reid Oldenburg
So that's another thing that we should be working on the next once to years.
00:37:02 Reid Oldenburg
There's no ICD-10 code for RIME.
00:37:04 Reid Oldenburg
And it's very hard to even identify cases.
00:37:06 Reid Oldenburg
And as you know, you've talked to a lot of different clinical researchers that if you don't have good data, it's hard to actually get a good message.
00:37:13 Reid Oldenburg
So I think we need to do a better job of
00:37:16 Reid Oldenburg
talking to the coders and engage with the responsible bodies like the CDC and actually have an ICD-10 code.
00:37:23 Reid Oldenburg
So these are some of the short-term things.
00:37:24 Reid Oldenburg
I mentioned the consensus guidelines and I think every one to two to three years we should probably be updating these consensus guidelines because RIME is a very actively moving field.
00:37:36 Reid Oldenburg
So in that sense, you know, I think that's going to be probably the mid-term goals for PeDRA is really continuing some of this work.
00:37:43 Reid Oldenburg
Of course, the basic science.
00:37:44 Reid Oldenburg
Thanks for giving me a chance to talk about some of
00:37:46 Reid Oldenburg
the basic science work.
00:37:47 Reid Oldenburg
I think the basic science work also in the midterm will be critical to continue.
00:37:52 Reid Oldenburg
And I think applying for larger funds from the NIH will really help answer some of these more mechanistic questions.
00:37:59 Reid Oldenburg
The third thing is I think we need to do more in
00:38:04 Reid Oldenburg
understanding and doing group collective efforts to look back and see what's happening in the drug-induced SGS and TN.
00:38:12 Reid Oldenburg
So Stephen Johnson's in toxic epidermal necrolysis.
00:38:15 Reid Oldenburg
And I think we need to do a better job of
00:38:17 Reid Oldenburg
of really looking at pediatric dermatology cases and looking retrospectively at outcomes and usage of different medications, because now there's some new data in the adult literature, and it's a little bit complicated because some of those patients were on immunomodulatory therapies for cancer therapy, but there's new data to suggest that JAK inhibitors may be very valuable for S-Jacintin.
00:38:41 Reid Oldenburg
And I think we need to start to
00:38:44 Reid Oldenburg
me to start to approach some of these questions that have been partially answered in the adult population and work to understand in pediatrics what, in our pediatric population, what is actually happening.
00:38:55 Reid Oldenburg
So I think that's a major question.
00:38:58 Reid Oldenburg
And then also, you know, just bringing in more ideas, bringing in our newer members, our younger faculty, our residents into the group to just bring more project ideas about medications in general.
00:39:10 Reid Oldenburg
You know, I think we have more work to do in
00:39:13 Reid Oldenburg
in urticarial dermatitis that may be triggered by medications, some of these other drug reactions.
00:39:21 Reid Oldenburg
And there's definitely a lot of opportunities.
00:39:23 Reid Oldenburg
So we definitely invite people to come to our sessions and engage with us online as well so that we can start to put our heads together to answer more things.
00:39:32 Reid Oldenburg
But yeah, good question.
00:39:35 Reid Oldenburg
More work is ongoing and more results to come, but we certainly have more work to do.
00:39:39 Reid Oldenburg
I don't think it's, I don't think it's ever gonna end.
00:39:42 Reid Oldenburg
I think we have so much things to look into.
00:39:45 Jenn Dawson
I think maybe I'll stop asking the futures question because it always is more work, more things that we need to do.
00:39:53 Jenn Dawson
We have more questions that need answering.
00:39:56 Jenn Dawson
But I think that the goals that you outlined there are really tremendous and highly achievable.
00:40:01 Jenn Dawson
And I'm so thankful that you are in the network and thinking about these things and getting others to think about them as well.
00:40:08 Jenn Dawson
One thing that I'm just personally curious about when it comes to you is, has there ever been
00:40:15 Jenn Dawson
like a publication or a study that you've come across that just totally flipped your thinking on something.
00:40:23 Reid Oldenburg
Yeah, and I think this really links up to some of the conversations, and it's not going to surprise you a lot of ways.
00:40:28 Reid Oldenburg
But in 2020, there was a paper where there was a patient that had a different severe cutaneous adverse reaction that we don't really cover in this discussion today called DRESS syndrome.
00:40:37 Reid Oldenburg
And that patient
00:40:39 Reid Oldenburg
was failing multiple therapies and had a very prolonged course and was on long-term systemic corticosteroids like prednisone.
00:40:46 Reid Oldenburg
And long-term prednisone, as many of our listeners know, it's not good for the body.
00:40:51 Reid Oldenburg
It causes metabolic dysfunction.
00:40:53 Reid Oldenburg
It's not good for bone density.
00:40:55 Reid Oldenburg
It has increased risks of infection.
00:40:57 Reid Oldenburg
So this patient was really suffering A lot.
00:40:59 Reid Oldenburg
And they did essentially, you know, what I've been talking about and what really excites me is they did some of these transcriptomics approaches and they identified the
00:41:09 Reid Oldenburg
inflammatory signature that was dysregulated in the patient.
00:41:13 Reid Oldenburg
And they ended up using an ex vivo preparation, meaning that they took the patient's cell out, they put it in a Petri dish, and then they treated it with a drug, and the drug worked in the Petri dish.
00:41:22 Reid Oldenburg
And then they actually, since the drug was FDA approved, they were able to use it off-label, of course, with extensive, this was at the NIH, by the way.
00:41:29 Reid Oldenburg
So of course, with extensive, you know, discussion with the patient and making sure everything ethically was okay, and they were using FDA approved dosing,
00:41:36 Reid Oldenburg
they were able to make the patient better using one of those small molecule JAK inhibitors.
00:41:40 Reid Oldenburg
And so that's just, to me, that's just like very mind-boggling.
00:41:43 Reid Oldenburg
And that happened in 2020.
00:41:45 Reid Oldenburg
And I think it was just like, it really was that sort of evidence of, you know, you can actually using these somewhat, that seem somewhat esoteric techniques, you can actually immediately turn around and help a patient.
00:41:59 Reid Oldenburg
So that was probably, that was the first thing that came to my mind when you said that.
00:42:02 Reid Oldenburg
But there's so many studies that are landmark and
00:42:06 Reid Oldenburg
groundbreaking as well.
00:42:08 Jenn Dawson
Well, thank you for letting me put you on the spot with that question.
00:42:11 Jenn Dawson
And I'm wondering for our listeners who are less familiar, if you could just give a quick description of dress syndrome.
00:42:18 Reid Oldenburg
Right, so DRESS syndrome is drug reaction with eosinophilia and systemic symptoms.
00:42:23 Reid Oldenburg
And this is another drug reaction.
00:42:25 Reid Oldenburg
So typically, you know, common things that cause DRESS syndrome would be an antibiotic and so, or an anti-epileptic, something that people are taking for seizures.
00:42:36 Reid Oldenburg
So after a few weeks, usually somewhere in the range of two to six, maybe 8 weeks, patients with dress develop organ damage in a rash.
00:42:45 Reid Oldenburg
So they get red, they get swelling of their head and neck.
00:42:49 Reid Oldenburg
And then in a lot of patients, they develop some type of organ damage.
00:42:53 Reid Oldenburg
Usually it's the liver or the kidneys.
00:42:55 Reid Oldenburg
And it's very scary.
00:42:56 Reid Oldenburg
And about 5 to 10%, but let's say 5% of patients, it actually can be fatal.
00:43:01 Reid Oldenburg
So it's really a scary thing in dermatology.
00:43:03 Reid Oldenburg
And we treat it by, of course, withdrawing the medication that caused it and then putting it on an adverse reaction list.
00:43:11 Reid Oldenburg
So never take it again.
00:43:12 Reid Oldenburg
Some of the patients get a bracelet.
00:43:13 Reid Oldenburg
Don't ever take it again, just like SGS and TM.
00:43:16 Reid Oldenburg
Don't take that medication again.
00:43:17 Reid Oldenburg
And then we treat it with immunomodulatory therapy, with the most common one being prednisone.
00:43:22 Reid Oldenburg
And the patients, they get, interestingly enough, they get very high eosinophil counts.
00:43:26 Reid Oldenburg
And we know that eosinophils are somewhat important because
00:43:31 Reid Oldenburg
if a biopsy is done in the skin or an organ like the heart or the liver, they can see eosinophils there as well.
00:43:37 Reid Oldenburg
And we know that also lymphocytes such as T-cells are really important as well.
00:43:41 Reid Oldenburg
And so the combination of this reaction with the medication and elevated T-cells in the blood and in the tissue is causing skin, but also organ damage.
00:43:52 Reid Oldenburg
So it's a really scary disease in dermatology and it's another severe cutaneous adverse reaction.
00:43:56 Jenn Dawson
The human body and our immune system never ceases to amaze me.
00:44:01 Reid Oldenburg
I mean, it's really amazing how our immune system has evolved to really, you know, prevent us from getting infection, but also the immune system is also preventing us from getting cancer.
00:44:11 Reid Oldenburg
You know, I heard recently that our immune system is maybe getting rid of 1 cancer a day in our body.
00:44:15 Reid Oldenburg
And I think it's,
00:44:17 Reid Oldenburg
It's really, it's not just the immune system, it's not just doing infections.
00:44:20 Reid Oldenburg
So it's really amazing that our immune system is able in so many situations to not go completely haywire and cause a lot of inflammation.
00:44:28 Reid Oldenburg
And of course, you know, the diseases in dermatology that we need to do better on is really understand how the inflammation
00:44:34 Reid Oldenburg
this dysregulated inflammation that's supposed to do the right thing is not working for us in certain disease states.
00:44:40 Reid Oldenburg
And I think that's where it's really, immunology is so fascinating in that way where you know that we need our immune system, but sometimes it can do the wrong thing, unfortunately.
00:44:49 Jenn Dawson
Yeah, sometimes our immune systems just get carried away.
00:44:53 Jenn Dawson
So thank goodness you and your colleagues are putting in so much time and effort to study this.
00:44:59 Jenn Dawson
thank you so much for joining me on Pedro Pearls today, Dr.
00:45:03 Jenn Dawson
Oldenburg.
00:45:04 Jenn Dawson
It's always a pleasure talking with you.
00:45:06 Jenn Dawson
I always learn so much.
00:45:07 Jenn Dawson
I hope others in the network and those who are listening feel the same way.
00:45:11 Jenn Dawson
Thank you so much for joining me.
00:45:14 Reid Oldenburg
Thank you so much.
00:45:15 Reid Oldenburg
Yeah, it was so fun to discuss with you and thanks for bringing such a fun discussion.
00:45:19 Reid Oldenburg
I really appreciate it.
00:45:25 Jenn Dawson
I'd like to take a moment to thank PeDRA's corporate council members.
00:45:29 Jenn Dawson
Our gold-level supporters are Eli Lilly and Sanofi and Regeneron Pharmaceuticals.
00:45:34 Jenn Dawson
Our silver-level supporters are AbbVie, Abeona Therapeutics, Arcutis Biotherapeutics, Chiesi, Incyte, Sanofi, and UCB.
00:45:46 Jenn Dawson
And our bronze-level supporters are DISC Medicine, Janssen, and Pfizer.
00:45:51 Jenn Dawson
We so appreciate their shared commitment to PeDRA's mission as members of the PeDRA Corporate Council.
00:45:58 Jenn Dawson
Thanks so much for listening to PeDRA Pearls.
00:46:00 Jenn Dawson
If you enjoyed this episode, be sure to follow us or subscribe to the PeDRA Pearls Podcast channel wherever you listen so you don't miss future conversations.
00:46:10 Jenn Dawson
To learn more about PeDRA and our work to advance research in pediatric dermatology, visit PeDRAresearch.org or follow us on social media @PeDRAResearch.
00:46:23 Jenn Dawson
Until next time, keep listening, learning, and collaborating to make a difference for kids with skin disease.