Pediatric Allergy & Immunology Program
Congratulations!
Congratulations on being selected for an interview at the University of Colorado/National Jewish Health Pediatric Allergy and Immunology Program! We are excited to meet you and introduce you to our program. For our Virtual Interview Day, this website will be a special supplemental resource for more detailed information about our program.
On behalf of the Department of Pediatrics, it's my pleasure to welcome you virtually to National Jewish and we look forward to meeting with you on your interview day.
In the meantime, take a look around our applicant website and get to know a little bit about one of the oldest Pediatric Allergy Fellowship programs in the country, whose graduates are throughout the world and are outstanding clinicians and excellent researchers.
We look forward to welcoming you to campus virtually in the near future and we'll see you soon.
Important Documents
University of Colorado Stipends
University of Colorado Program Training Agreement
National Residency Matching Program (NRMP) requirements
COVID-19 Vaccination Requirement and Compliance
GME Eligibility and Selection Policy
GME Work Environment Policy
Prospective Resident Benefits Summary
Diversity Matters
Program Aims and Objective
Eligibility for Specialty Board Exam Information
Program Overview Presentation
Employment Background Checks
Drug Screening Policy
Informational Videos About Our Program
Below you will find a couple videos that will give you just a glimpse of what our program and our city have to offer you.
National Jewish Health is the leading respiratory hospital in the nation.
Our patients come from around the world seeking cutting-edge, comprehensive and coordinated care. At National Jewish Health we provide thorough, multidisciplinary care tailored to the needs of the individual. We dedicate the time and the resources necessary to provide the right diagnosis and treatment. We rank in the top 5% of funding from the National Institutes of Health. Through the years, National Jewish Health clinical and translational researchers have made many groundbreaking discoveries. Including the discovery of IgE, the molecule responsible for allergic reactions, and the discovery of the T cell receptor which plays a crucial role in recognizing foreign invaders and orchestrating an immune response. As a leading institution in the treatment and research of respiratory, cardiac and immune related disorders, National Jewish Health has always been dedicated to educating future generations of health care providers and their patients.
The Myla High City boasts more than 300 days of sunshine a year. Denver offers unparalleled opportunities for outdoor recreation, a thriving cultural scene, diverse neighborhoods and natural beauty. National Jewish Health is the only facility in the world dedicated exclusively to groundbreaking medical research and treatment of patients with respiratory, cardiac, immune, and related disorders.
At National Jewish Health, at National Jewish Health, at National Jewish Health, breathing science is life.
Meet Our Pediatric Allergy and Immunology Training Faculty
Hi there, welcome to National Jewish Health.
I'm Elizabeth Gayorkis, I'm a physician assistant and I've been working here in the day program for the last 27 years.
I love my job, I love working with all the fellows. The first year that you're here, you're down here in the day program and you're working with me and Alex Phillips, the other physician assistant that I job share with and there's a lot of learning that goes on.
So it really is a family here, very supportive atmosphere. I hope you enjoy your visit here and your interviews and feel free to send me an email or ask any questions that you may have. I hope to see you again soon, thanks, bye.
Hi, I'm BJ Lancer, Director of Pediatric Allergy and Immunology Fellowship Program here at National Jewish Health in Denver.
I came to Denver to start my fellowship here seven years ago and remained on faculty.
The reason I chose this program was because of the people and though some of the faces have changed, I remain here today and I'm happy to be a part of this program and happy to be at National Jewish because of the people.
I have had a tremendous education and a tremendous opportunity to work together with my friends and colleagues.
I spend most of my time seeing patients with food allergies and doing a lot of different challenges and spending my time in clinical research on food allergies as well.
So balancing my time between food allergies and the fellowship program keeps me busy and keeps me happy here and I look forward to the opportunity to work together with you as a fellow in the future.
Hi everyone, my name is Kara Santos and I'm on faculty here at National Jewish and I'm also a proud alumna of the class of 2014.
I am in clinic full time and I have the pleasure of seeing both pediatric and adult patients in my practice and I also have the pleasure of working with almost all of the fellows on the adult and pediatric side, both as a clinic preceptor and as a mentor.
So I hope you consider our program very highly. It truly is an excellent place to train and I guarantee you that you'll get a great depth of experience and Denver is also a really fun and exciting place to live.
If you have any questions about our program or living in Denver, please don't hesitate to email me at santosc.njhealth.org and I wish you all the best of luck on the interview trail.
Hi, I'm Jessica. I am MedPete trained and came here to National Jewish for Fellowship and continued on with my fellowship research project to pursue a third year of fellowship on my research interests of origins of allergy. So I dabble a little bit in the lab, have some grants for that and also do clinical research where I'm a co-investigator of some of our birth cohort studies that we do here.
I'm really just so happy to be here on faculty, just as a former fellow, now faculty. It's been a seamless transition and I just love the people here. Also the head of the fellowship wellness committee.
Here at National Jewish, we very much value work-life balance and really taking care of our fellows.
So we're excited about this program and the different events and measures that we have in place for the year ahead.
And related to wellness, we live in one of the best cities in the world. Denver is wonderful.
We have so many things to do, so many activities to pursue, just being able to look out and see mountains everywhere.
It's really just such a perk to be able to live and work in such a wonderful city.
Hi everyone, welcome to National Jewish. I am so happy that you're here looking at the premier fellowship for allergy, pediatric allergy immunology, I think in the nation.
I am former director of the fellowship, so I'm a little bit biased. My name is Nathan Rubinovich, I'm now the clinical director.
I've been here for a while, 25 years, and I started off as a fellow in the program and you'll find that a lot of our faculty actually did start off as fellows in our program.
If you're looking for a comprehensive education where you're going to be able to handle pretty much anything that comes your way from the most kind of bread and butter allergy immunology to the most severe, you'll get it here.
You'll get hands on education and a kind of very academic type of approach from the attendings. What I mean by that is that they're not just going to tell you what to do, but they're going to tell you why it's important to do it, what the mechanisms are, so you kind of really get into the integrity of the reasons why you do what you do.
I love that part of the fellowship, just the teaching part, and we all love to teach for sure. I love the fact that you have this kind of behavioral health component that really makes a difference for our patients and teaches really the fellows how to handle some of the more difficult behavioral issues which are going to be bound to come up in pediatric allergy.
I love the fact that we're all friendly and nice and informal kind of type of feeling, which I think is nice for the fellows.
We do feel like we're one big family. And of course, then you have Denver, which you can't beat Denver. So we're happy you're here, at least by Zoom. So welcome to all of you by Zoom, and we hope you'll get a chance to be here physically and see our beautiful city and our fantastic fellowship.
Thanks so much. Bye bye.
Greetings.
I am Donald Leung, division head of pediatric allergy immunology.
I'm glad that you're looking at our program.
It is one of the only programs that is in an institution that is not only the number one respiratory hospital in the United States, but focuses on research in allergy and clinical immunology.
I've been here now for over 30 years and been extremely excited about the developments in the field of allergy and immunology during this time frame.
And during that time, we've mentored over 50 fellows who have gone on to have successful careers.
Our own research has to do with the origins of allergy. We are now following several birth cohorts to determine why people get allergy. We've already made significant advances in understanding why people get atopic dermatitis and food allergy.
I hope you will join our fellowship and the exciting developments going on in our institution.
Hi, everyone.
I'm Mark Boginevich.
I am professor in the division of allergy immunology in the Department of Pediatrics at National Jewish Health and the University of Colorado School of Medicine.
I've been at National Jewish now for a little over 30 years.
My research and clinical interests are in atopic dermatitis and welcome to my mass.
As you can see, ignore the golf balls and focus on the diplomas and plaques.
Actually, the ones I'm most proud of are the teaching awards that have been bestowed on me by our illustrious fellows.
So I hope I get to meet you all in person in the near future and stay well.
Hi, I'm Kieran Gentilly.
I am a nurse practitioner in the Pediatric Day Program.
The Pediatric Day Program is a very unique program where people come from all over the country, sometimes all over the world, to help diagnose very difficult and challenging allergy, immunologic, and sometimes pulmonary conditions that their local specialist may not have been able to help with or just needs a little assistance with.
We are the last resort, so families come here very stressed. By the end, they're always, I've never seen an unhappy customer, and it's the most rewarding experience because you get to give them answers that they've been waiting years to hear.
And hearing it from the best in the nation is such a relief for most of these families.
So we work alongside the fellows.
Elizabeth, my partner, and I work alongside the fellows to split and divide the patients and help, and we make sure that we're always giving you the best educational experience possible.
There's a ton of teaching and education that goes on in the Day Program.
I love working in the Day Program because I've been in healthcare 20 years now, never seen anything quite like it.
And you almost always save lives or positively impact lives, so it's really an amazing place to work.
I look forward to getting to meet all of you guys and hope that you find National Jewish to be a top contender for you.
Thanks so much.
Meet a Few Former Fellows
Bryce Hoffman
My name is Bryce Hoffman. I graduated from National Jewish in 2019, and now I work for Kaiser Permanente in San Francisco. My favorite part of fellowship was definitely the day program. Having the chance to see the most complex cases from around the country and heal them day by day was really one of a kind, and it made my job now so much easier because I have no trouble seeing the toughest cases here in the Bay Area. I chose National Jewish because it seemed like the most robust program with the peds and adult tracks, the incredible legacy, and the passion of the faculty was really contagious. So I think it was the best decision. I would not create for anything else, and I hope you're able to join our family.
Divya Chauhan
Hi, everyone. My name is Divya Chauhan, formerly Divya J. Raman, and I was a National Jewish Allergy Fellow from 2015 to 2017. I chose National Jewish Pediatric Allergy Fellowship because it was a unique program, unlike anything I had ever seen before, especially with the day program. And I figured that being trained to see the worst of the worst patients would help me see anybody in clinic, regardless of the type of job I chose afterwards. I ended up going to the University of Utah where I was faculty for about a year and a half, and then I moved back to Colorado and started again at National Jewish. I think that the most beneficial thing about the program is really, you really change people's lives with learning unbelievable eczema care, food allergy management, and I am currently seeing patients now that I used to follow in fellowship who are still so grateful for the care that they received. So, National Jewish's fellowship program was the best decision I ever made, and I feel so grateful and so honored that I was trained here, and I'm very happy to be back.
Neeme Zaddy
All right, guys, my name is Neeme Zaddy, and I graduated from NJ in 2018. I currently work as an academic physician at the Children's Hospital of Los Angeles, and I can tell you right now that if you want to be at the forefront, and I mean the top of evidence-based medicine, and really be prepared for anything clinically, you gotta go to NJ. Trust me, we get referrals from everywhere, and I can tell you we even get referrals from other allergists, and every time I'm like, wow, I really feel comfortable with what I know and what I can figure out because I got a really amazing base working at NJ. I can tell you a few things that I really like about the place. Number one, the people are awesome, especially the faculty, and BJ is really awesome. He was my mentor when I was there. You couldn't ask for better program director. Really, I have like a million shoutouts, but I'm gonna just keep it there and let you guys know that really, you should go to NJ. Okay, bye.
Melissa Robinson
Hi, everyone. My name is Melissa Robinson. I graduated from the fellowship program in 2018. Currently, I'm working in private practice in the Chicagoland area. On my interview day, I was really impressed by all the hands-on training that they offer. You get to see the day-to-day easy cases, but you also get to see a lot of complex cases. You have the opportunity to make a difference and see those results. You work so closely with the faculty and the staff there. They're all so nice, and very well-educated, and come from a high caliber of allergists. The fellows were truly happy on my interview day, which was important to me in terms of work-life balance. National Jewish Health really prepared me well working in practice. When I was looking for a job, I had a lot of opportunities. Everybody in the area is really impressed with where we get our training from. You know, National Jewish Health has a really strong name in the allergy community in terms of being well-trained and well-educated, so that was nice to have that opportunity.
During practice as well, I felt really confident being able to see the easy cases, the really complex cases, just based on what I was doing and seeing in fellowship. My favorite part of fellowship, it was nice coming from a bigger fellowship, having a lot of people to work with, kind of going through the same thing with you. I also really liked the day programs. You work with patients for the one or two weeks that they're there, so you really see the results that you might not see in an outpatient or private practice setting. You know, the idea of living in Colorado was also pretty cool to myself and my husband.
Fellowship Training at the University of Colorado School of Medicine
On my feet
I feel the game
Yeah, with you, I can feel it again
You never had me, you said you were lonely
I was a lonely soul, but that's the only
Long time coming since I've seen your face
It's happened everywhere by trying to replace everything
That I broke till my feet went numb
Praying like a fool, just shot a gun
Heart's still beating, but it's not working
It's like a hundred thousand voices that just can't sing
I reach down, trying to love, but I feel nothing
Oh, my heart is numb
But with you, I feel it again
Yeah, with you, I can feel it again
You never had me, you said you were lonely
I was a lonely soul, but that's the only
Long time coming since I've seen your face
It's happened everywhere by trying to replace everything
That I broke till my feet went numb
Praying like a fool, just shot a gun
Heart's still beating, but it's not working
It's like a hundred thousand voices that just can't sing
I reach down, trying to love, but I feel nothing
Oh, my heart is numb
But with you, I feel it again
Yeah, with you, I can feel it again
Yeah, with you, I feel it again
Yeah, with you, I can feel it again
You never had me, you said you were lonely
I was a lonely soul, but that's the only
You never had me, you said you were lonely
I was a lonely soul, but that's the only
You never had me, you said you were lonely
I was a lonely soul, but that's the only
Get a Glimpse of our Many Pediatric Allergy and Immunology Conferences
All right, so I'm going to be talking about a patient who presents the day program with a three-year history of a rash. A quick overview is we're going to go over the HPI differential, kind of our plan and diagnostic evaluation.
I'm going to take a quick pause at the differential diagnosis and see if anybody has any thoughts or comments, and then I'm going to kind of walk through my thought process with the top items in our differential, kind of look at the immunologic mechanisms behind those, and then our final diagnosis and the literature review of what this patient was ultimately diagnosed with.
So chief complaint is we had a 13-year-old young man that presented with a three-year history of rash over his lower extremities. So the history of the present illness is, you know, this rash started approximately three years ago.
He was seen by his pediatrician at that time and was diagnosed with scabies. They did put him on a course of permethrin, but it ultimately didn't resolve the rash. And then the rash started migrating to his lower extremities, like predominantly behind his calves and along his shin, then also involving the top part of his foot.
He was seen actually by multiple different dermatologists, and the latest dermatologist had diagnosed him with atopic dermatitis and then pure agronodularis. They had tried multiple topical steroid creams, used on a class II for a period of time, did bleach baths, oatmeal baths, did tacrolimus as well. Nothing seemed to help the rash. At some point, he even tried doing a gluten-free diet and didn't resolve the rash. His current skin regimen, when he came to us, as he was moisturizing with like gold bond once every two to three days, he showered every two to three days, didn't take any baths. He did switch up his soap and use like an unscented laundry detergent. Nothing made a difference. And really the biggest thing is he was just excessively scratching, bleeding, had skin breakage, and a lot of trouble with sleeping because he was just scratching all the time. In terms of systemic symptoms, other than his sleep, he was just kind of fatigued and tired throughout the day as well, but no fevers, unintentional weight loss or other symptoms apart from that. His past medical history, he had some history of mild allergic rhinitis. Family history, just his father had a mild atopic derm. The biological mother's history is unknown, so he lived with his mother or stepmother and biological father. He's going into eighth grade, loved video games. That's what he did most of the time, using the PCU on his computer. So a physical exam for him is his skin. He had plaques with pretty irregular border scaling, erythema, and definitely a lot of excortation on his lower legs and then on his feet, but the rash did spare his soles.
He had some significant cirrhosis and like henification, no weeping lesions, but definitely like some dry blood. No pustules or vesicles, no palmar hyperlinearity, and then his hair and nails were normal. These are actual pictures from when he first presented the day program. I apologize for the lighting.
It was a little more impressive in person, but you can see just kind of these thick plaques that he had over the medial aspects of his feet here and then on his lower legs on both sides.
He had this on the back side of his calves as well. These would completely scab over, off and on. He's just really, really scratching. Our patient was diagnosed with atopic dermatitis, so I just pulled this from the practice book parameter update in 2012.
Just to kind of highlight, he was diagnosed, we're doing a management of atopic dermatitis. His management's not successful. He's not had any improvement over three years, and so we're at that point now reassessing is this diagnosis of atopic dermatitis correct?
At this point, I'd like to open it up before I kind of reveal what our differential diagnosis and see if anybody had any thoughts. Evelyn, are you on? Chair, did you say if the dog had fleas or not? The history is consistent with popularity carrier. The lesions to me don't look like atopic dermatitis, particularly because it's primarily involving the lower extremities, and popularity carrier frequently involves lower extremities. Was the dog evaluated for fleas? That's a good question. I did not ask that question, so I'm unsure. That's interesting, Chad. You mentioned that the dermatologist had diagnosed him with prurigo nodularis, right? Yes, sir. What would be your comment to that diagnosis looking at this patient? I think a neurodermatitis definitely is on the differential with the success of scratching, although his lesions were more plaque-like, lichenified, not what I would expect from a prurigo nodularis, it wasn't nodular. Exactly. If you look at some of the studies with prurigo, you need to have symmetrical upper extremity lesions to even be included in a trial. This patient clearly has a very different looking sort of look to these lesions. I think that what jumps to mind, I don't want to jump ahead since I saw this patient with you, but since nobody seems to be jumping on, including our illustrious fellow, Dr. Wang, who saw this patient with me, Evelyn, are you there? Yeah, I'm here. Okay, good. Well, clearly Evelyn and I looked at this and we agreed, like Donald, that this did not look like typical atopic dermatitis. Some of the features you would point out that don't fit for a typical atopic dermatitis was what? It started three years ago in a 13-year-old, it started in the inguinal region, a region that is often spared even in our totally involved patients who have sparing of the groin region.
We thought that some of these lesions maybe had a numular look to them, a psoriatic look to them, although if you went back to the pictures, you would say it's not the typical scaling that you see in a psoriatic plaque, so a little less specific. And also the nails didn't have very many, no pitting of the nails, and the location for psoriasis was a little unusual, he said he had some arthritis when he wrestled, but mom kind of chalked that up to the fact that he exercises a lot, whether it was true arthritis or muscle aches and pains, and there were no joint findings either on his physical exam.
The reason he was on a gluten-free diet was the concern of dermatitis or pediformis, but he had been checked out for celiac disease before, and that was all negative, and we did check that again. Chad, did you mention they treated for scabies? They did, yeah. I believe you got a couple of rounds of permethrin, and there really wasn't any significant difference after treatment. Obviously, they look like scabies. Ideally, you would want to do a scraping if you're really not sure, but you want to treat rather than just subject this patient to a course of, especially if you're a dermatologist. Chad, I just wanted to ask, when it started three years ago, was there anything in particular that happened during that onset? Was there any change that he started to stop lacrosse and skateboarding or any certain exposures during that time when it started? Not that I recall, no. No illness associated with it as well when it all started? No. Unless, Evelyn, you remember differently, I don't remember any kind of triggering event for him. No, there was nothing. And then for the rash, it just progressively got worse. There wasn't any seasonality to it or anything like that? Yeah, no, that's a great question. There was no seasonality to his rash. In fact, it was just so bad summer and winter, even during the summertime, he'd be wearing pants to cover up because he was embarrassed about it. Chad, can you hear me? This is Flavia. I can. Okay, sorry. Do you mind pulling up the picture again for us? Oh, yeah, absolutely. I haven't seen kids in a while, but could it be like a lichen planus type presentation? I don't know if you see that a lot or at all in teenagers, but. Yeah, I mean, I think that was definitely something we were thinking about or that was on the differential. It can be seen in adolescents, it just didn't seem consistent with the distribution, I think was our main thought. But what is, I think the lichen planus idea is a good one, Flavia, but usually involves the trunk. I'm just wondering what involves just the lower extremities. That's why I'm still intrigued by papilloticaria, because this is definitely not atopic dermatitis. If you were to biopsy this, I'm not saying you should, but how would papilloticaria look as opposed to numinal eczema that Dr. Bogdanovich is thinking about, which also tends to affect the trunk as well as the extremities. If you have somebody who only has lower extremity, I think you still have to put contact dermatitis in this differential, although it doesn't look like contact.
What would the biopsies, generally we don't biopsy dermatitis because the lymphocytic infiltrates, but what do you think a papilloticaria might look like that would separate it from these other differentials? I guess if I had to theorize for a papilloticaria, I think that you'd have a predominantly mass cell response with lots of histamine and then soft tissue swelling, and then maybe not as much of a, like if we were comparing it to atopic dermatitis, for example, you wouldn't see as much of an impact on the keratinocyte differentiation, and for plaque psoriasis, we wouldn't have the predominant like TH17 response, although I have to go back and look at skin biopsy for psoriasis, but with those thick plaques and probably like some hyperkeratosis as well. Is that what you were looking for? No, you're too fancy. Papilloticaria classically is due to fleabite reactions, and actually you see a eosinophil infiltrate, which even though we say atopic dermatitis has eosinophils, you almost never see intact eosinophils in atopic dermatitis. You can stain for it, but it looks like a little bit like a vasculitis. I mean, you probably wet-wrapped him and he got better, I assume. We actually recommended a different course, so when Evelyn and I saw him, you know, history was not atopic really. He had no history of skin infections. What's striking when you look at this patient is how normal his skin is other than these lesions that clearly he has created. So when you take that history, you hear that the parent suspects that this child spends a lot of time scratching. To us, what was really needed was a biopsy to clearly tell us whether this was the neurodermatitis that we were thinking about versus possibly a neurodermatitis associated with something like psoriasis, but less likely.
Did you scrape for tinnia at all? Did anyone ever scrape for tinnia or you just didn't feel it was tinnia? Yeah, bilateral multiple lesions that would just arise where he scratched and then they would heal up, so it didn't have that sort of progression. So Chad, now that you're into the immunology, if somebody had parigo nodularis, which cytokine would be excessively elevated in that lesion? If you could do a PCR or immunohistology on that lesion, which you probably didn't do when you did biopsy, but what would you have seen that's being studied now for biologics? Which is the itch cytokine? Oh, IL- 2. No, not IL-2. Oh, well there's IL-33. Two down from 33. 31. So IL-31 is the main cytokine from type II cells that causes itching, although IL-4 and 13 can cause itching also, and that's what disappears often with the polymer treatment. But IL-31 is being studied also for excessive itching. It's very high in parigo nodularis. That would be on the boards if they were going to ask a question about parigo nodularis.
Okay. Yeah, I had actually read an article about the pathophysiology itching, and I was going to talk about this later on in the presentation, but they had listed IL-2 as one of the cytokines for itching, and then also tachykinins as well. So parigo nodularis is IL-31 predominant. So I guess we'll keep moving. So this is just kind of, I know that we were talking about atopic dermatitis was less than a differential, and these are in no particular order for these patients, but this is the top seven that we had come up with for this patient at the time. So our plan for him is, you know, we're going to get labs. We wanted to go ahead and proceed with the skin biopsy just given the irregular distribution of his rash. We ended up sending him to the dermatologist for evaluation of that skin biopsy, look at doing a psychological evaluation, and then
a sleep study. So I'm going to quickly kind of go over the labs that we obtained for him. So we had gotten a CBC, which was normal. He did not have an elevated eosinophil count. Given the concern for potential psoriasis, we had checked inflammatory markers, ANA, RF, and HLA-B27. Those were all negative. We were also thinking potentially, is this like a weird presentation of MCAS, which is significant psoriasis, and he also had some dermatographism, but those urinary markers and triptase were negative. His thyroid studies were normal. CNP was normal. We checked a vitamin D level for him, and just given the concern for his diagnosis of atopic dermatitis, the association of low vitamin D associated with eczema, he didn't
have low vitamin D. And then with his significant poor sleep, we checked his ferritin, which was
low as well. His celiac panel, like Evelyn had mentioned, had already been checked in the past, and that was negative. We checked his T cell subsets because one of the things we were thinking about is this like a cutaneous T cell lymphoma, and his T cell subsets were normal, although that wouldn't rule out a mycosis fungoides. Really, you need a skin biopsy for that. We checked a TH1, TH2 cytokine panel, and those were, the TH1 was normal. His TH2 cytokine panel, which I'll go over in the next slide, had some abnormalities. His wound culture was positive for staph aureus, but was merciless negative. Given his excessive fatigue, we also checked the AM cortisol for him, and it was normal, and his total IG level was normal. His TH2 cytokine panel showed elevation of his IL-4, IL-5, and IL-6. We were expecting his TH2
cytokine panel would be normal and maybe point us more towards a TH1 or other response. That was a little surprising, especially given the marked elevation of his IL-4. That would be something maybe we can discuss in a little bit. Looking back at the differential, three of the things that we crossed off were the thyroid disease, celiac disease, and the mast cell activation syndrome. The patient also had a... Chad, before you go on. Yes, sir. Another board question might be, what do you see in dermatodermatitis or pediformis? What is on the skin biopsy? I don't know what they did with the skin biopsy. What did they do? Did they just look at H&E, or what did they do? They actually did stain for a fungal stain. That was the only other stain that they used. What would you look at? There wasn't any immunofluorescence, right? You didn't send for immunofluorescence. We did not know. Yeah, but on the boards, they asked what immunoglobulin deposition you might see in dermatitis or pediformis. IGA? Yeah, IGA, and what kind of cells do you see infiltrating in? I mean, DH would be a good differential because it's a very, very... It's much itchier than atopic dermatitis. Yeah, it's extremely puritic. What cell type would you see in DH that you wouldn't see in prurigo nodularis? Probably neutrophils. Yeah, those are the two features of it that you need to be aware of retaking boards. Okay, thank you. He had multiple stressors. Like I said, he was pretty uncomfortable, embarrassed with his rash, had a history of ADHD, and then there was a lot of stress in relationship with his parents. Both, and Jennifer, if you don't mind touching on this later on,
he lived with his biological father and stepmother, and they reported were pretty hard on them at home, so that was definitely a source of stress for him. He ended up doing biofeedback therapy, and he really enjoyed that part of his stay here. Also saw a psychiatry on Dr. Weiss as well. So like we discussed, we did send him to dermatology for a biopsy, and on the visit to the dermatologist, he was diagnosed with psoriasis, recommended starting on stelara, and skin biopsy was not performed at that time. So yeah, parents were pretty upset after that visit. This was like their third dermatological opinion, and there wasn't any further testing. So in terms of the differential diagnosis after the dermatology visit, it really was unchanged in our opinion. So for the sake of time, I'm going to skip over this slide. I just thought that this was a really cool article that came out in Jackie a few months ago looking at mechanisms of skin autoimmunity and kind of grouping them into different subsets, so I'm going to skip over that. So I just wanted to kind of go through my thought process of our top four items in the differential and look at the
underlying immune factors for them. So looking at the practice parameter update for atopic dermatitis that came out in 2012, talks about the distribution again. This patient didn't necessarily fit the typical picture for eczema. There's different skin conditions, this article talked about, that can mimic atopic dermatitis, and then in situations in which the diagnosis obvious, skin biopsy should be considered, which is the point that we were at for this patient. Then looking at the underlying immunology for atopic dermatitis and the major cytokines involved, and the barrier dysfunction, subsequent triggering of the epithelial release of different cytokines, including the IL-1 beta, IL-33, activation of Langerhans cells, dendritic cells, then subsequent activation or TH2 response, and those are the cytokines involved there. Obviously, I didn't go back and read it for the IL-31 being the predominant cytokine, and then one of the
major things with the atopic dermatitis as compared to psoriasis was the atopic dermatitis, you have that decrease in the antimicrobial peptides and increased risk for infection or colonization with staph aureus. Then looking at our next one on the differential was psoriasis, just in general effects to 3% of people in the US. It's primarily a T cell mediated disease with high levels of IL-17 and IL-23 produced by your TH17 T cells. One-third of those patients go on to develop psoriatic arthritis, so again, that's why we were checking some of those inflammatory markers in ANA. Then just the Stellara that was recommended by the dermatologist was that antagonist of the P40 subunit by IL-12 and IL-23. I won't spend too much time on this slide because I want to make sure we have enough time for continued discussion, but I just really enjoyed this slide looking at the underlying immunology for psoriasis. Then like I'd mentioned earlier, comparing eczema to psoriasis. In psoriasis, as a result of your IL-17 stimulation of your epithelial cells, you have increased production of your antimicrobial peptides, increasing your innate immunity. Also, you're producing the CXC chemokines that are recruiting more neutrophils to these lesions. It's a little bit more atypical for psoriatic lesions to become infected as compared to your atopic dermatitis lesions. Then this is just looking at this feed-forward cycle and development of the psoriatic plaques with the stimulation of your Th17 cells and release of your IL-17 cytokine. The next item on our differential was the mycosis fungoides. It's the most common form of the primary cutaneous T cell lymphomas. I hadn't realized prior to researching mycosis fungoides, but Cesare syndrome is more of a systemic version of this, where you get these T cells circulating. Then you also have erythroderma is one of the classic features of Cesare syndrome. Looking at the distribution of mycosis fungoides, it's often a periodic of therminous patches in non-sun exposed areas, which is not consistent with our patient. That's primarily that CD4, CD45, the memory T lymphocyte response. I just had looked up a skin biopsy since we had gotten a biopsy for our patient for mycosis fungoides.
There's some characteristic findings in here. You get these atypical lymphocytes. They have these cerebriform nuclei with clear cytoplasm surrounding them. These are called like halor cells or halo cells. Then you can also get these micro abscesses as well. The fourth item on our differential was the perigonodularis or lichen simplex chronicus, pointing more towards the lichen simplex chronicus as we discussed earlier, just given the characteristic of the lesions. Treatment for lichen simplex chronicus is the
topical steroids and technolinius, but then also addressing the underlying psychologic factors is that's a huge part and can't be underestimated for lichen simplex chronicus. This is not our patient's actual biopsy, but this is the official read. The histologic features of that of lichen simplex chronicus are revolving perigonodular, indicative of chronic rubbing or other trauma. I also mentioned that there's some chronic non-specific inflammation in the dermis and an underlying low-grade dermatitis may be contributing. Some of the classic features that you can see on biopsy for lichen simplex chronicus is this hyperkeratosis and then this hypergranulosis area as well. After the skin biopsy, we had diagnosed our patient with lichen simplex chronicus or another name for that is neurodermatitis. Given that he had these thicker plaques on his legs, we ended up doing mometazone BID to his leg lesions.
We had done what we had actually started wet wrap therapy during his stay in the PCU, but he did not respond significantly to it. It helped a little bit. I think it was probably more so also contributing to the fact that he wasn't able to scratch as much because we were covering up those lesions. We did schedule psychology and psychiatric follow-up for him and Dr. Weiss had started him on gabapentin and started him at a low dose, which a max dose for him that he was prescribed was up to 300 milligrams a day. We started him on iron or vitamin D. The big thing for this patient was that the gabapentin is what really, really helped him. After starting on gabapentin over the course of the following week, his itch totally subsided. I followed up with the family and two in the four weeks after discharge and at four weeks, he only had two lesions remaining and was no longer itching. That was just a really good case. I just wanted to talk about lichen simplex chronicus briefly, the pathophysiology of itching, and then a couple
case reports looking at gabapentin for itching and why we think it may work. Like I said, lichen simplex chronicus is that chronic skin condition that's strongly linked with emotional factors. It's developed typically on areas that are accessible on the body. Like for our patient, he was scratching all over his legs. It can be a very vicious cycle with lichen simplex chronicus. It's just that itch scratch cycle, but the importance or the therapy is skin care and then psychological care as well.
This is the article I had looked up on the pathophysiology of itching. One of the interesting things that it looked at was that there's both a central and peripheral component to itching. It talked about the opioid mu receptors being more of the central component of itch and then the different intermediaries over here. Cytokines will cross that off and put interleukin 31 and then tachykinins in particular was CGRP because that's one of the tachykinins that's theorized to be impacted when treating with gabapentin. This was a study that was done with more of a bench research study on rats and then impact on gabapentin and pregabalin on the release of substance P and CGRP. The way that they checked for this is they induced inflammation by injecting a rat's paw with Freud's adjuvant and then five days later they subsequently deceased the rats and then dissected their spinal cords and then were looking at levels of substance P and CGRP and then impacts on the levels from gabapentin and pregabalin. What they found is if there was inflammation associated with it then the gabapentin and the pregabalin decreased the CGRP release. Then a couple just like brief case studies on gabapentin. This study looked at only at two patients and it was a puritis of unknown etiology. They had tried a lot of different treatment modalities for the itch and were unsuccessful. They were started on gabapentin and their dosing was started at 300 milligrams and they went all the way up to 1800 milligrams a day for these patients which was really high but both of them subsequently had resolution of their itch. This study looked at actually nine patients with pyrigonadularis and lichen simplex chronicus and treatment with gabapentin. They treated anywhere from four to ten months and then continued to follow these patients for an additional three months after they stopped treatment.
What they found is that six out of nine patients had complete remission after that study period. So gabapentin seemed to work for but again I think there's a lot of studies that still need to be done in regards to gabapentin because most of it like I said is just small case studies. But the way that they were theorizing is that gabapentin secondarily inhibits release of the CGRP. Secondarily increase of GABA from the afferent neurons and then also modulating the new opioid receptor so also having a central component. Again their starting dose was a little bit higher. They started at 300 milligrams a day and up to 900 milligrams a day I believe for this study and our patient again was started at 50 milligrams a day which and he went up to about 150 milligrams per day which ended up being successful for him. So kind of the takeaway point was for this patient was that importance of that mind-body connection that itch-scratch cycle and that the treatment of the lichen simplex chronicus involves that two-prong approach of skin care and psychotherapy and then if the diagnosis is in doubt you know making sure we're broadening our differential and considering a skin biopsy because ultimately the skin performing a skin biopsy really I thought helped kind of nail down the differential for this patient.
And kind of some of the discussion points or whatever anybody else wants to talk about you know is this patient did have elevation of his THC cytokines in particular his IL-4. Not quite sure how to interpret that in this case and then you know hypnosis or self-hypnosis is a big modality recommended for the psychological treatment so you know kind of a curiosity is like why would that break the itch-scratch cycle you know what's the role of skin biopsies in these patients you know if we had ended up starting on a biologic after the diagnosis of psoriasis outside dermatologists you know would it have worked you know I'm not not 100% sure we didn't have IL-17 or IL-23 levels but I'd imagine not and then you know gabapentin dosing it's all over the place but I think gabapentin just needs to be some more studies need to be hashed out before it becomes a regular treatment for itching so and then those are my my references and those are my kids going to school so yeah I'll open it up to see anybody who wants to talk about anything. Well I just want to say Chad you did a phenomenal job so thank you very much this is supposed to be your informal I think we could actually upgrade you to a formal presentation so there you go. I think what's interesting about this is just how sure the dermatologist was that this is psoriasis and kind of walked in two seconds later psoriasis Galera here's the you know here's what you got to do can I do a but I'm not even going to do a biopsy because I'm so sure that this is correct but sometimes I guess you gotta you gotta keep on you know digging sometimes in this case I think the biopsy was actually in the end the most informative for us so anyway good good great presentation. So just to jump in Nathan you know what's disappointing really is that you know is the you know approach of many dermatologists so this person had seen several dermatologists before coming wasn't responding to their treatments still didn't have a biopsy and this is a recurrent theme that some of us who have been around here for a few years now have seen over the 30 years of patients coming to the day program with rash that hasn't responded and never biopsied and some of those patients have turned out to have had EBV lymphoma have had mycosis fungoides have had dermatitis herpetiformis and it's just shocking that and with this particular dermatologist in fact she's made the diagnosis of psoriasis and put patients on biologic who you know so this wasn't the first one that was recommended for a psoriasis biologic therapy so you know it's just hard to understand why they wouldn't want to make a definitive diagnosis because one of the problems that we run into is then patients get put in clinical trials and we've seen this in adult onset atopic dermatitis supposedly who turn out to have you know other diseases especially you're concerned about cutaneous T cell lymphoma and now are being treated with a new study drug and then the study drug turns out to be you know blamed for their wrong diagnosis so that's one of the many problems that we encounter i have a question um as far as the presentation of this patient uh is it typically typical for like in simplest chronicus simplex chronicus to present us if it's spreading and bilateral or it is more likely for it to be more focal where they're sort of kind of scratching at the same area or maybe even the the um outer surface of the thighs you know where they typically can reach and scratch more um chronically it's just i guess that was kind of what threw you know me off with the fact that the presentation seemed to be inner side of the feet of both feet and then it spread up to um both uh legs both um lower extremities so i don't know dr bogey nevich are you is that something that's that was pretty typical of like in simplex one you would say look um uh lsc so like in simplex chronicus neurodermatitis most often seen in adults so this was a younger patient to begin with right that person will typically pick a spot that they want to scratch at but certainly patients have been described with a bilateral presentation and i think the important thing is that this is not um the lesion of parigo nodularis as we discussed earlier um and yeah i mean if the person is you know um invested in scratching because of obsessive compulsive disorder stressors and so on they can create these lesions you know in in different places but it's always in you know these lesions are places that they can easily reach so you almost never see this you know on their back for example and in our patient in particular he would constantly scratch his legs with his feet as well the the the needle aspect of his foot mom is a substance abuser who'd been in and out and then terminated her rights and a stepmom adopted him legally um but he wasn't opposed to that he likes his stepmom but felt very judged and stressed and ridiculed and his adhd wasn't addressed so i think as he got older and more expectations were put upon him and he wasn't able to successfully meet their expectations because of his adhd there just became a lot more there developed a lot more tension and negativity in the parent-child relationship um and it was really clear his his mom couldn't really um say anything positive to him without there being a negative attached to it so we worked on addressing his adhd and thinking differently about how they establish expectations give him directions um you know help him and support him with school rather than just expecting him to be able to do multiple step more complicated activities that he wasn't capable of and then we also focused on sleep because he was a very sleep deprived kiddo which of course makes us all more stressed and irritable and anxious anyway so we worked on sleep we worked on the parent-child dynamic and it took a little while to get parents comfortable with the idea of um seeing dr wise they weren't initially on board with the idea of treating the adhd or even the gabapentin because it to them was more of a psych med and they ended up not wanting to medically address the adhd but were comfortable with the gabapentin fortunately so recommendations going home are further assessment and intervention around his adhd and then family therapy um with him i did introduce the self-hypnosis and it was actually really interesting because he came in and was doing the cricket feet where he was just constantly rubbing the top of his other foot without even realizing he was doing it and we introduced the self-hypnosis he got to a relaxed state and then he quickly fell asleep but everything ceased so despite parents talking about he scratches all through the night he actually stopped scratching once he was actually calm and settled and then uh ched i don't know if there was any final outcome because the other thing was his breathing was really unusual once he fell asleep and he was having disrupted sleep that i don't think was all related to the itching so we tried to get a sleep study and couldn't get one here i don't know if they followed up on that they did so when i talked with mom a couple weeks ago they had scheduled the sleep study for the end of august and then also the psychiatric follow-up good good so i'm glad they stayed on top of those things that i was um intrigued because i saw the team that you guys decided to order these uh t1 t2 cytokine profiles i wonder if dr leong you know we normally don't even get those in our clinical research trials don't know how good measuring these commercial assays for peripheral um cytokines don't you know i i don't think those results are even legitimate right because i've never detected i04 in the circulation was that was that plasma that was sent or was it lymphocytes what was the biopsy it was not it was not biopsy it was plasma yeah you almost never see i04 in systemic circulation so i just question you didn't send any control plasma so we don't know if they always detect i04 i think the gallopentin was very really fascinating if it's true but you know that the placebo effect in atopic dermatitis is almost 50 percent so just dr b going into the room can probably eliminate itching in these people so you know a multiple things were done uh the most important thing of course was breaking the itch-scratch cycle because he's leading me i started just the pope effect i would love to see a controlled study act of gallopentin because this is the first time i've ever seen this dramatic an effect but you should find a authored paper not by malcolm greaves who edited a book with me 30 years ago he's probably over 80 now uh i would probably look at brian kim uh he's the itch expert in he's the itch expert in united states and you would probably find i031 in one of his tables but very good job chad i think you have a lot of good teaching points here although i still think it'd be worth checking if the dog has fleas because the history is consistent with papillotic area thank you sir also as a note uh fleece can jump no more than two feet off the ground so if those lesions are below two feet it's possible that he does have fleas at home and may have been the reason why it all got started i don't know i guess yeah it could be the trigger and if he has trigger and if he has carpeting and he likes to lie on the floor in shorts watching tv or something it could have spread more than two feet but i think on is right on about that oh yeah great job uh chad actually question is there in a way we could find out how many of our day program patients have been put on gallopentin for the chronic itching because i do recall um of a day program patient that i uh ended up taking care of a couple years ago just also was put on gallopentin by dr weiss um and a week primarily in patients who have pain so you know we have those patients who present who can't even walk because of the severity of their atopic germ on their lower extremities and brian has really helped us with gallopentin in those patients where pain is the predominant feature it's just for sleep and some too hasn't he well it definitely does help with that for sure and when nothing else sleep wise is helping and then it would be easy to do everything you know search the research database and you could get account pretty quickly okay migraines also by the way gallopentin good job yeah keep in mind great job thank you as chad pointed out in the beginning you know it's important to see them in follow-up you know we have that in the day program but the clinic you need to see them back too to make sure they're responding nice job thanks everyone thank you.
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