[00:00:02] Introduction: Welcome to All Cats Considered, a podcast from the Feline Veterinary Medical Association. Here we interview professionals from across the veterinary world and take deep dives into the latest evidence based research, developments, studies and guidelines that improve feline health and well being. We are the home for veterinary professionals seeking to enhance the care of cats through high standards of practice, continuing education and evidence based medicine. In each episode you'll hear interviews with a variety of experts in our field covering a wide range of topics and the latest developments in feline health. We'll share the key points you need to know to improve your patients care.
Let's dive in and listen to this week's experts.
[00:00:45] Kelly St. Denis: Hi, I am Dr. Kelly St. Denis, co editor of the Journal of Feline Medicine and Surgery and Journal of Feline Medicine Surgery Open Reports and today we are meeting with Dr. Frane Banovic to discuss the Clinical Spotlight articles that he's written for the Journal of Feline Medicine and Surgery, Feline Immune Mediated Skin Disorders. And in this episode we're going to be discussing Part one. And I should mention of course that we also have two other authors on the article who have not been able to join us today. Dr. Fran, would you introduce those individuals for us as well?
[00:01:20] Frane Banovic: Absolutely. Good morning. Thank you for the invitation for this webinar. Basically my two colleagues are Dr. Paolo Gomez, he's a board certified dermatologist and Dr. Karen Trainor, she's a board certified Veterinary Pathologist with a special focus on dermatopathology.
[00:01:38] Kelly St. Denis: Very cool. Thank you and I appreciate you so much. And I wondered if you could start also by telling us a little bit about yourself, how you got into vet medicine. Sometimes we have some really good stories come out in these podcasts. And also what what sparked you to go into dermatology in general sense?
[00:01:55] Frane Banovic: I did my undergrad at a veterinary school in Zagreb in Croatia. I did my vet school at University of Zagreb in Croatia. We do not have theoretically undergrad and grad school like in the US So we generally go directly to a veterinary school which is a six year duration. I am currently an Associate professor of Veterinary Dermatology at University of Georgia College of Veterinary Medicine. I finished my vet school in Zagreb in Croatia in 2008, after which I enrolled in a PhD program with a focus on veterinary Dermatology and then went on to finish a rotating internship at University Ludwig Maximilian University in Munich at the veterinary school there and went on to further finish a residency in Investigative Veterinary Dermatology at North Carolina State University in 2011. After that I stayed to do a fellowship in veterinary investigative dermatology. Before I joined University of Georgia College of Veterinary Medicine as an Assistant Professor In 2015, what drew me to veterinary medicine in general, I have always wanted to be able to help animals and to be able to do my job in a way that I can advance their health and their diseases and their knowledge as well as the owners abilities to try to treat these diseases. Specifically in veterinary dermatology I was always interested to understand processes and veterinary dermatology is very unique in that way compared to many other specialties is that we have the largest organ from all organs and at the same time we are able to visualize things. That means in veterinary dermatology we go to a very, very depth processes to understand why a certain disease develops, why certain cells are involved in certain diseases, who calls who, how do they communicate. And all of that is generally available to us because we can relatively easily collect the samples compared to other specialties. That's one of the things that is really beautiful is to combine generally the basics of immunology together with seeing basically patients with the diseases and be able to understand why are they getting affected by these diseases and how can we manage these diseases better.
[00:04:21] Kelly St. Denis: That's amazing. I guess I'd stop to think about it for a minute like that. It makes a lot of sense. It's one of those, like you said, you can see what's going on and it's a lot, It's a lot. It's not easier. Dermatology is not easier because there's so many complex processes. But it's nice that it can be right in front of you and, and you can investigate accordingly. So thank you and again welcome and I just wanted to let our listeners know that we're talking about part one today of the article Feline immune mediated skin disorders. So we had to decide at when at the inception of these articles that there are so many mediated skin disorders in cats that we decided to break it into two different clinical spotlight articles. I remember having that conversation with you that really it doesn't all fit. So today the conversation around part one is going to look at the diseases that are covered in that part one which are feline immune mediated cutaneous diseases of pemphigus complex, lupus erythematosis and thymoma and non thymoma associated exfoliative dermatitis.
But just from a general perspective, Dr. Banovic, I was wondering if you could just discuss with us like how common are immune mediated diseases in cats?
[00:05:32] Frane Banovic: Very good question. So in general rule there is always debate about Using terminology of autoimmune and immune mediated as disease processes. In general sense, we prefer to use autoimmune when we can really show that there is a direct immune response against its own tissue, against its own antigen, which we would call autoantigen. Unfortunately, in veterinary diseases or veterinary medicine, the advancements of techniques generally lacks the human field. So in many instances we have a high suspicion that there is an autoantigen, but we generally lack techniques or studies to prove that. So many times the we like to use the terminology immune mediated diseases, which shows that there is an inflammatory process. Highly likely it's autoimmune in many of these cases. But unfortunately, due to the lack of studies, we cannot really come and say, oh, this is an autoimmune disease. We show that this is an autoantigen. And if you look at the dogs and cats, we have far more evidence in dogs than we would have. Because in general sense, I would also say as a, as a clinician scientist, we tend to research less cats than we do dogs.
[00:06:47] Kelly St. Denis: And that's so true.
[00:06:48] Frane Banovic: And also, to be honest, I would also say that it's not as easy to collect samples from cats as it is from dogs, which also contributes to the problematic.
Now, regarding these diseases, how common they are, it's a very good point. Well, I would say that in my clinic, the most common disease we tend to see is some kind of an allergic, allergic dermatitis disease, whether that's feline atopic skin syndrome or atopic skin syndrome due to food. I would say that's rare. And then we do see these weird immune mediated diseases come to us on a regular basis. Some of them come through ER because the cats have undiagnosed pemphigus, that is not an allergic skin disease, but gets treated like that and then unfortunately comes through emergency service because the patient is not doing well. Some diseases are not that dramatic and it's just a foot pad and therefore you can wait a month or two months to get a referral in. So it just depends on the patient. But do we see them? Absolutely, yes. As a matter of fact, to give you a fun story, one of my PhD students last week emailed me foot pad lesions from her roommate's cat. And the cat has what we would call plasma cell pododermatitis. It's in the part two, but classic example of it. All four feet or all four central pads. And of course, so they do. They are there, but maybe they are not diagnosed. Maybe sometimes there's not such morbidity that people are going to Investigate more in depth and multiple factors.
[00:08:22] Kelly St. Denis: Yeah, yeah. And so as clinicians like someone for myself in general practice, obviously there's some pretty classic things that we may see that say immune mediated dermatologic issues or autoimmune dermatologic issues. But when I'm looking at a cat with skin disease, or would you say there's a short list of things you would say we should put that autoimmune disease on our differential list as soon as possible or right away?
[00:08:47] Frane Banovic: Well, there are some clues like in the paper that is the reason why we, why we kind of decided to go into the paper project. Because some diseases definitively have a very relatively unique clinical phenotype. So. Or pemphigus, that would be. For instance, there are not many diseases that will cause very uniquely the nail fold production of pus in the air. And when you squeeze the nail folds out, you basically see pus coming out. That's very unique for pemphigus foliaceous in cats. There are not many differentials that will do that same thing with for instance, plasma cell pododermatitis. Very unique to affect the central footpaths of multiple eggs. So there are not many diseases that will do that. So they do have some uniqueness. Sometimes it may be a little bit tricky, but definitively, if the patient is not responding after multiple weeks of treatment, whatever the clinician thinks it is, it is advisable to obtain good quality images and consult with a veterinary dermatologist, which probably can be done in a different ways through emails or however the clinics are providing these consults. I believe all over the world, wherever there is access, there is my email likely. And if any anyone has questions or needs help is more than welcome to email me and utilize the email that is given as a correspondence. Absolutely. We always want to try to help so that to, to raise the awareness of these diseases to help people diagnose them better.
[00:10:20] Kelly St. Denis: I really love that now, now we can do that with digital imaging, get images even just from the client to the veterinarian, then to a specialist dermatologist.
Get a better sense of where we're going with something given the history.
And just to focus in then on penthagus foliaceous. Now that is listed as being probably the most common autoimmune skin disease in cats. And you know, we have that classic, as we were taught in school years ago, the pinniplanum pad affected lesions. But I noticed that in this article you also described some other areas that are affected with pemphigus in some cats like the pa, the face, periola perioli, areolar regions and closkin folds, as you noted. So can you tell us a little bit more about those areas and how they might be affected?
[00:11:06] Frane Banovic: Well, what we do not know exactly is why certain areas in the body with certain diseases are affected more.
Others we have our suspicions with some diseases. And somewhere if it's an allergic disease, there is a potentially the idea that the allergens come closer in contact with certain areas on the body where there is maybe less hair, like interdigital areas or ventral abdomen. There are some theories that potentially the density of muscles is much higher in ears and maybe higher in those areas on the body where you have an allergic response with autoimmunity or immune mediated. We really are unsure. We are unsure why exactly the nail fold in a cat and not commonly in a dog. There is some theory, and it's coming out slowly, that because the disease affects certain molecules in desmosomes, which are adhesion molecules, it is believed that certain areas in the body may be enriched in these desmosomes or have higher density of desmosomes per square meter of the skin. And it's possible that in those areas you have more desmosomes and therefore you are seeing higher response. That's just a theory we do not truly know. But interestingly, it is very common in certain areas and when it comes back, it likes to come back in certain areas.
So we do think that there has to be an immunological and probably anatomical reason for that.
Now, the recurrence of lesions, we do believe that stems a little bit from the memory cells that are generally called T memory resident cells, and likely they tend to remember to help induce the immune response and orient the autoantibody production. But it is interesting, for sure, that the disease likes to tackle certain areas. And cats are a bit different than dogs, of course. And that's what we are pointing out in the paper.
[00:13:01] Kelly St. Denis: Yeah, exactly. And so you mentioned lesions coming back and. And for the most part, most, I think most of us probably feel that steroids are going to be something that we're going to use for treatment for a long time. I diagnosed a cat that was only a year and a half years of age, not that long ago. And is that like a lifelong thing? You talked about lesions coming back maybe after the steroids are stopped. Do any cats go into full, like remission and never have recurrence?
[00:13:27] Frane Banovic: Yeah. So treatment wise, what we have known now in the last, I would say three decades is that absolutely that the glucocorticoids remain the mainstay of treatment for many patients because relatively they tend to work on all the disease process development of the autoantibodies. They work very well on tissue inflammation where we see a lot of neutrophil activation, sometimes eosinophils, they are great at shutting down T cells and B cells and antigen presentation or the autoantigen presentation tend to be the fastest to achieve meaningful clinical remission. And at the same time also the ones that are available relatively cheaply to everyone in the world. But what we also know now, and this is compiling data from multiple case series basically. Unfortunately, we don't have some kind of a center for autoimmune diseases where we have multi institutional studies where we compare and collect data. We generally every center published their own data in, you know, that's kind of. We do not have a like in the US like an nih, A main, main above us in the human medicine world where institution basically collects people once a year and tries to get a sense that everyone contributes the data so that we can see, you know, what's the prevalence of remission, what's the prevalence of recurrence of disease. But our experience tells us that many cats will relapse that rarely. We are going to see a cat that is just given, let's say glucocorticoids and it goes into remission and it never comes back. It can happen, but it's rare. Now, considering that other medications we like to use as steroid sparing agents because glucocorticoids will have a lot of side effects. These other medications, steroid sparing agents like cyclosporine or chlorambucil, mycophenolate, et cetera, they do require a long time to really achieve meaningful suppression of the T cells and to some point some of them B cells. That means that we need to extend our glucocorticoids continuously if we are not starting these medications at the same time. So these days I would say that the standard of care in dogs and cats with pemphigus is probably to initiate steroid sparing agents immediately with glucocorticoids so that the side effects of leukocorticoids will not be there in that patient long term because of overusage of the drugs. That is probably the standard of care. I would say it's not written anywhere in textbooks or anything like that. But that's how I would say the vast majority of dermatologists will practice today.
[00:16:10] Kelly St. Denis: Right. Okay, thank You. Yeah, it's always difficult when you have young cats like that, especially because you don't want them to be on steroids for such a long period of time. Right. If it's going to be the rest of their life, what, what options do we kind of consider?
[00:16:23] Frane Banovic: Correct. That's why we, we, we would do the steroid sparing agents so we can wean off the glucocorticoids. And once we see that the disease is controlled, still without glucocorticoids, we will proceed and start weaning off the other steroid sparing agents.
[00:16:37] Kelly St. Denis: Right.
[00:16:37] Frane Banovic: So the end result is the least amount of medicine we would need to use would be the best for all of us.
[00:16:43] Kelly St. Denis: Yeah. Good. Thank you. And then, you know, I was wondering about diagnosis because this is something that with pemphigus, you know, they used to always tell us. And again, I'm, I'm dating my terms of when I graduated from vet college, but it was always about waiting for the pustules and only biopsying pustules. But I really like in this article that you guys discuss cytology that can be done and it isn't always just about sampling from pustules. And I wondered if you could tell us a little bit about that from a practical perspective in clinic.
[00:17:11] Frane Banovic: Absolutely.
[00:17:11] Kelly St. Denis: So.
[00:17:12] Frane Banovic: So there is a little bit debate even among the dermatologists here, how we should approach this, largely because we are dermatologists. So we just see the skin cases. And for us to diagnose our cat with pemphigus is, to some point, if we see these cases all the time, relatively easy. The problem becomes is that we have to provide advice to clinicians who are not dermatologists, that they tend to see all the organs and all the diseases associated with that. So in these instances, we are kind of always troubled how to make a recommendation. Why do I say this? We utilize skin cytology a lot to diagnose pen figures because we can see the acantolytic keratinocytes, which are very unique for the disease. And with the clinical presentation of the nasal bridge and the ear pinna and the nail fold, we generally don't tend to see many differentials for that, such as potentially like a pyoderma, staph infections with exfoliative toxins that can also cause acantolytic keratinocytes, we rarely see that presentation of pyoderma in cats. So therefore, when we see a patient like that, and if we do a cytology and we can see these acantolytic keratinocytes surrounded by neutrophils. We are very much probably, I would say above 99% certain that we are dealing with pemphigus foliations in a cat. Now, ideally we would go ahead and biopsy that, but then it depends where the lesions are. And for instance, some lesions, some cats with pemphigus uniquely have only lesions in the nail fold. So there are different phenotypes of the disease. Not everyone is generalized. So in that you would have to remove the whole toe. So and that's where it gets a bit tricky, I would say that the vast majority of us tends to then call the PEM figures based on a clinical presentation, history and cytology findings. Of course, if we can, we will go ahead and do biopsy. Now, we are dermatologists, so for us this is what we do every day of the month. Now, if we take someone who sees this rarely as a private practitioner, they may lean more towards biopsy to make sure that we get what we need. Yes, ideally we would sample pustules, but they are relatively short lived on the patient's dogs and cats, predominantly because of the rather thinner epidermis. So they don't tend to stay. So what you end up having is usually crusts. Now if you see some erythema beneath it tells you that probably it's still an active process. We tend to go and try to get those most recent lesions that the owner can remember and that we see that there is still erythema. If the crust has no erythema and you can just pull it off, then likely it's already gone. What we never want to do is scrub the crusts away. So we always want to submit the crust because the acantolytic keratinocytes usually are embedded in them. If you do any surgical scrubbing, you will lose that diagnostic sample and your biopsy will come back as inconclusive. Meaning they don't know what it's an inflammatory process, but they don't know exactly what's going on.
[00:20:17] Kelly St. Denis: And that's one of the key things that again are pointed out in a box out in your article about taking biopsies and not prepping the skin or shaving or anything, because you're taking away a lot of that diagnostic information.
[00:20:29] Frane Banovic: We rarely will ever need to scrub the skin, exceptionally rarely. So I would rather not do that on any patient. Unless you want to lose your diagnostics and the biopsies are expensive. You need rather a heavy sedation for a cat than a dog. You do not want to repeat these processes multiple Times. So it's better when you do it that you do it the best way you can.
[00:20:55] Kelly St. Denis: So, technical question for you. In the discussion around surgical, where we might be heavily sedating or using a full anesthesia, do you recommend or discourage the use of local blocks underneath or around the area so that the cat has less discomfort when they wake up?
[00:21:11] Frane Banovic: Yeah, we always use the local blocks. Just the key is to do a sub Q block. So we will inject subcutaneously. Of course, most commonly lidocaine. Sometimes we have lidocaine with epinephrine or adrenaline, depending how you call it, depending on a continent. We always do local. The only thing is we do not want to do like intradermal injections or anything. So it needs to be subq. So we numb the skin and we wait few minutes until it's completely numbed before we absolutely take that. Yeah, so we always do that. And yes, and then you have to be a bit careful. Where are you going to put a cone on or you're going to protect those suture areas so that the cat doesn't rip up the sutures and stuff like that? In many patients we don't have these issues and generally they tolerate it. I would say majority tolerates this very well. In our experience with biopsies, they seem to.
[00:21:59] Kelly St. Denis: Yeah, yeah, I agree. Well, thank you so much. I mean, we had so many things to talk about about different diseases in this podcast, but we've actually already reached our time. So I just wanted take a moment to say thank you again for this amazing article and to tell our listeners, definitely, you want to go and get this article. All of our articles on the Journal of Feline Medicine and Surgery are available open access. You don't have to go behind a paywall or anything like that. So you can have access to that article. You can download it and use it as a reference for your clinic. You know, when you next time you see those derm cases and you're trying to remember what should I do if I think this is autoimmune? Have a look at these articles. And in our next podcast, we're going to be talking about part two, which covers a number of other autoimmune diseases. So, Dr. Bonovich, thank you so much for joining us today and I look forward to seeing you next time.
[00:22:47] Frane Banovic: Thank you, Kelly. Thank you for asking us to contribute to these articles.
[00:22:51] Outro: Thank you for listening to this episode of All Cats Considered. We hope you enjoyed this interview. For more information on the topics discussed in this episode, please head over to catvets.com podcast podcasts and explore the links in the show notes. Don't forget to subscribe to this podcast on your platform of choice so you won't miss any episodes as we release them. Have thoughts or ideas about the interview you heard today? Share them with us by leaving a comment on our Facebook page or shoot us an
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