[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] Dr. Kelly St. Denis: Hi, I'm Dr. Kelly St. Denis, co-editor of the Journal of Feline Medicine and Surgery and Journal of Feline Medicine and Surgery Open Reports and I'm here today for part two of my discussion with Dr. Frane Banovic. He is an Associate Professor of Veterinary Dermatology in the Department of Small Animal Medicine and Surgery at the University of Georgia College of Veterinary Medicine and we are discussing part two of a Clinical Spotlight article, Feline Immune Mediated skin disorders. Welcome Dr. Banovic.
[00:01:16] Frane Banovic: Thank you, thank you. Pleasure to be here today. Regarding this webinar on the Part two.
[00:01:21] Dr. Kelly St. Denis: So we've been discussing in our previous podcast about some of the common diseases such as pemphigus foliaceous and we had a lot of good discussion around general tips for general practitioners dealing with skin diseases that might be autoimmune. And we're going to look at a few other diseases today.
But I also like to always find out about our authors a little bit more. And last time you told us about your veterinary background, how you got into vet medicine and dermatology and today I was wondering if you could just tell us a little bit about your research focus because I noticed in your Bio and Georgia site that it's quite interesting.
[00:01:57] Frane Banovic: In general sense, the main focus of our lab, which is we call our lab a comparative inflammatory skin lab, is to investigate inflammatory skin diseases across species and relatively to compare our results to the human diseases. Reason for that is that in human inflammatory skin diseases the advancements are far better or faster than what we see in veterinary medicine, specifically dermatology.
So when we try to investigate disease, we like to use a lot of the human counterpart to understand exactly what they do and how much they have moved in a certain field. And then we try to reapply that to the veterinary inflammatory skin diseases.
The reason why we do this is because largely we live now in a time of so called precision medicine where we would like to develop so called TAR targeted treatments where we target a single molecule or a single protein, single receptor in a disease process and try to reverse the pathology. That's a bit contrasting the old dogmatic approach where we treated every disease with a very broad non specific immunomodulators.
So that has advanced our understanding of the diseases. And therefore these days you have the monoclonal antibodies for many diseases and other small molecular inhibitors that we see in veterinary dermatology. And we actually advance the field far more than any other specialty just because we are understanding better the skin diseases.
Our main focus remains the allergic skin diseases largely because they are the most prevalent disease that affects across species. That means dogs and cats and we see it as well in horses.
And also I will be honest and say that's where the majority of our funding comes from to investigate these diseases.
Now in the background I have always had a great interest in autoimmune immune mediated other diseases that we tend to see as well. And so generally the funding for these diseases is far less than the funding or the most common diseases because they are very rare. And generally rare diseases in veterinary medicine do not get the same funding and appreciation like the most common one.
So in that case, for instance, you will see that the vast majority of papers coming out in veterinary dermatology are related to allergic skin diseases versus an autoimmune skin disease. Our interest remains the same.
We truly appreciate some of the help we got for some autoimmune diseases from foundations such as the Shelley and Colti and Coley foundation to investigate canine familial dermatomyositis.
So there are. And now we are investigating cutaneous lupus in Coleys and Schultes through the help of the foundation. So we do get some ability and it's something that we always were founding very interesting these diseases. So however, the large focus is still remaining to be allergic skin disease. There are generally majority of our funding for my PhD student, my grad students, master students is coming from.
[00:05:09] Dr. Kelly St. Denis: Thank you. I really find all of that very interesting and I think I mentioned as we were talking before our podcast that my background is in human medicine in juvenile diabetes, which is also an autoimmune disease. So I find your studies quite interesting just from that perspective as well.
So as our listeners might be aware from the last podcast, if you listen, the articles are covering a number of autoimmune immune mediated diseases in cats and we did talk about pemphigus foliaceous last time, but there were lots of other Diseases covered in that article.
Part two of the Clinical Spotlight article looks at erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis spectrum.
And then alopecia areata, plasma cell pododermatitis, all the fun ones, and then proliferative necrotizing otitis externa. So some really interesting characters in that group. And I think you've also got auricular chondritis in there as well.
And some of our listeners may be saying, hey, I remember I had a case of that. And they may not be very common, but I think a lot of us have had one or two cases of some of these diseases at some point in our career. One of the things that I really noticed about the first three that you talk about, the erythema multiforme and the SJS and 10 spectrum is the overlap in the diseases. And although EM used to be sort of described as part of that syndrome. Can you tell us a little bit about EM versus erythromultiformin versus the other syndromes that what makes them different?
[00:06:39] Frane Banovic: What we have issues with is a little bit, we like to copy paste the human terminology, right. Sometimes the diseases in humans, when you compare them to the veterinary world, they are very much alike and there is no doubt about it. But sometimes some things are a little bit weird and different.
Chemo multiforme in humans is most commonly infectious in nature.
That means there is usually a herpes virus. So you get a human herpes virus, let's say on your lips, and that virus, somehow the viral particles from that area get transmitted to your skin, on your thighs and on your hands and suddenly you get these weird so called target lesions with three concentric rings. Yeah, that's the classic example of erythema multiforme. If we do try to compare that in dogs and cats, we rarely see these classic target lesions.
But do we have herpes in dogs and cats? Yeah, predominantly more pathogenic in cats because of how it's in the respiratory areas.
And could it be then causing this reaction? Yes, there were a few case reports. Unfortunately we don't have large case series.
Now sometimes people have always thought that erythema multiforme can also be a drug reaction. And that's where it gets confusing because when you have a respiratory virus, it's very common that they will give the patient some antibiotics and then it becomes a challenging perspective to understand if the skin disease would have developed even without those antibiotics or not, or is it truly antibiotic induced.
And that's the whole confusion because the Steven Johnson syndrome and toxic epidermal necrolysis are proposed to be in majority of cases, drug reactions.
So if you suspect a drug, then you start suspecting, oh, could it be drug erythema multiforme or drug Steven Johnson toxic epidermal necrolysis. And that gets a bit really uncertain in some cases. Unfortunately, we just do not have techniques where we, let's say, take blood cells and put them together, culture them with the drug to see if the blood cells like T cells will proliferate like they do in humans, to show drug reactions or releases of cytokines like interferons and stuff like that. We just don't have that capability. And, you know, cat is very small, so you cannot just take 10ccs of blood in a sick cat. So therefore we many times will just presume that there could have been a drug, there could have been a herpes. We are unsure histologically. The reactions will look sometimes very similar and cannot be differentiated. So we rely on clinical times.
Steven Johnson should be more macular, so there will be patches and epidermal sloughing on the other side. The erythema multiforme potentially sometimes can be erosive as well, but it doesn't tend to affect such body percentage areas like the Steven Johnson and toxic epidermal necrolysis. But nonetheless, I have to be honest, sometimes there's possibly even an overlap that it's going to be a hard call which disease you're going to call histologically. You cannot just, you cannot diagnose these diseases as one entity or the other. Histology is suggestive of both entities. And that's one of our problems that we have.
[00:09:58] Dr. Kelly St. Denis: Right.
[00:09:58] Frane Banovic: And so, yeah, the only way to circumvent this more would be to get more published cases where we could then start comparing in depth like we do in dogs, and then try to find the differences clinically to see, you know, can we tell clinicians better, okay, this fits this better. This fits this better entity.
[00:10:19] Dr. Kelly St. Denis: And so if we've only have two cases published of related to feline herpes virus in em, is that something that clinicians should be worried about? Like, if we're dealing with a potential diagnosis, should they be starting a CAT on famciclovir? If they have a specific pattern of lesions, like, where, where would they go with that while they're waiting for pathology results?
[00:10:39] Frane Banovic: Fantastic. So usually the pathology results, at least in my setting, maybe it's a bit faster setting than usual, but within three to four days, you generally will see some results coming Back to you. Preliminary or full report.
And I think worldwide, every lab is working generally faster. The issue is we actually had a case, very, very unique case two, three weeks ago where we were actually dealing with a respiratory infection that was treated and then the skin lesions started developing with ulcerations, erosions, as well as exfoliative dermatitis. And we absolutely suspect that it is highly likely an erythema multiforme reaction. But could we now a hundred percent say it's not a drug reaction because there was a respiratory virus and then it was given some antibiotics? We do not know. But treatment wise, probably if the patient will tolerate, we would treat for both. We would dampen the immune response towards keratinocytes so they are not getting targeted by cytotoxic T cells. And at the same time we would probably treat the virus just to protect ourselves. So the least, least amount of viral load in the patient would probably produce less immune attack against keratinocytes. So we would just protect ourselves. But there is no great consensus on this. So what I do may, you know, someone else may be doing differently somewhere in the world as a dermatologist. So I'm just basing this, like I said, we are many people see this, but they may not publish the cases.
So we just don't have enough data. Now if we get 20, 30 cases published, then we can already start thinking about what best outcome measure, you know, is because of this treatment or that treatment.
[00:12:24] Dr. Kelly St. Denis: Yep. This might be another good argument for not using antibiotics in hyper respiratory tract infections that appear to be viral in origin.
[00:12:33] Frane Banovic: I, that is, you know, many times, I mean, I am unsure to, to be honest, I don't see these cases and what the current recommendation is, whether they suspect it could be mycoplasma or whether they think it could be herpes or they are many times guessing.
I really do not know. Our patient had the classic eye changes, the oral ulcers, and then it started developing the other skin lesions. So we really for sure think that it was an immune reaction. We do not see the viral particles in the skin lesions on the biopsy because it's not a herpes infection with the virus. It's just probably some immune response to the virus that overspills on the, the keratinocytes. But the classic IHC staining, immunohistochemistry staining we do for the virus and skin lesions. The virus is not there. We do not see the ballooning degeneration of the keratinocytes and the classic or cytopathic effect of the Virus.
[00:13:30] Dr. Kelly St. Denis: Now what was said in there about also potentially finding DNA particles or acid from the virus?
[00:13:37] Frane Banovic: Yeah, we have tried to research that in dogs and we cannot find these in immune mediated erythema of multiforme.
We may not have the correct primers or our technique may not be sensitive enough, but there is probably some kind of a tiny DNA particle there. We just cannot find it. We just. At this stage, probably no one researches this disease because it's so relatively rarer.
So it just stays there. And we tend to treat both arms the suspicion of herpes at the same time as the suppression of the immune system and then hoping that it will all go away once we suppress and then it will not come back. Hopefully.
[00:14:18] Dr. Kelly St. Denis: Again, thank you, that's very helpful. And I guess we should highlight too that that's only in situations where we think there was a herpes virus in the first place. Right. Like EM is going to present in different presentations distribution of lesions that won't necessarily suggest that we need.
[00:14:35] Frane Banovic: So I mean if people suspect that there is a drug and there is a good, you know, there are some different scales that can be used for drug causality. But if you. We suspect clearly that the drug is causing this, the reaction usually develops within like 4, 5, 8 days of instilling that drug. Absolutely, you should stop the drug. We are not saying that it cannot be caused by that. However, we just don't have the same methodology to prove the drug reaction. So we rely a lot on, you know, we treat it. But then again there was always a virus. So theoretically we don't know which is first.
[00:15:11] Dr. Kelly St. Denis: Right.
Sometimes that's frustrating.
[00:15:14] Frane Banovic: Absolutely.
[00:15:15] Dr. Kelly St. Denis: And then when you talk about drugs and looking aside from erythema multiforme, but to the syndrome Stevens-Johnson and toxic epidermal necrolysis, there's a very short list of drugs that we might think be related to that. I wondered if you could talk about that those three and then sort of is there.
[00:15:36] Frane Banovic: We definitively have more cases of dogs this year we had probably two or three cases of Stevens-Johnson coming through the coming in toxic epidermal necrolysis coming to the ER. Key here for clinicians is that these. This is basically the same disease at different severity categorization. So in theory the best thing would be to call these diseases epidermal necrolysis diseases stage 1, 2, 3, just like we call the burn patients stage 1, 2, 3.
But due to the classic old names and when we used to give the names of a disease per clinicians that have discovered these names, these names tend to stay. But in theory, Stevens-Johnson and toxic epidermal necrolysis is the same disease, except one is a milder stage or the mildest of all. The other one is the most severe form. Now, the drugs are proposed to be the most common reasons why you get this disease. And among the drug classes, we have far more evidence. Of course, in humans they can even do genetic screening and they can tell you that they are not going to give you this NSAID because of your genetic background, because there's a good chance you're going to get a drug reaction to this. In dogs, we already know that the beta lactams are common. We see some NSAIDs and then we see also TMS drugs, trimethoprim sulfa antibiotics. We really stopped using these a lot, you know, when they were very popular in 80s, 90s, when people were giving them, then I would think they were. They probably had more drug reactions and not just to the skin. The tms, from, you know, clinical hypothyroidism to everything else, it can do many things.
In cats, I would say it's really rare for us to document that means again, we see some cases, but we suspect usually beta lactams because they are commonly given to cats.
In humans, for instance, tetracyclines like doxycycline rarely are seen with this syndrome. But there are so little cases of cats published with this that it's very hard to make, I would say in depth conclusion that we can say, but I would expect the same drugs. Luckily, we don't use TMS in cats, rarely, at least we as a dermatologist, maybe when we treat nocardia or some rare infectious diseases, we do not. Betalactams on the other side are commonly used for many things.
So you just have to pay attention to that. And absolutely. If I was using beta lactam and I would start seeing epidermal sloughing skin with epidermis peeling off I would immediately stop the drug and transition to something that's not related to that in here.
[00:18:12] Dr. Kelly St. Denis: Because it's a spectrum and like you said, it can be sort of early disease and advanced. It's described as a medical emergency for some patients if they're in that sort of mid to advanced level. And I found it interesting, if you stop the drug, it doesn't necessarily mean that the whole process isn't advancing and the cats are potentially at risk.
[00:18:32] Frane Banovic: Yes, absolutely. So the same thing is the principle in dogs and as well as in humans. Once you have taken the drugs, the drugs have metabolites and the drugs have Half lives just because you stopped it. Today there is an immune response.
This is a big debate in humans whether they should give you immunosuppressors or not. The problem was that majority of these patients in humans would go through the burn centers. And when they go through the burn centers, the burn centers are probably the best equipped people to deal with widespread epidermal sloughing.
Problem is this is not a burn. Burn is a one time insult. This is an immune attack on keratinocytes and it does not stop.
Now, who usually runs the burn centers in the last 30 years or 40 years or before that are usually surgeons. And surgeons are generally not very fond of using immunosuppressive drugs with burn patients, which is basically logical. But again, these are immune mediated attacks against keratinocytes, your epithelial cells. So therefore there is an immune response. So probably the consensus today, and there are no great studies on this, is that you should use immunomodulators to suppress the reaction because it's going to keep on continuing for a few days possibly. And if the extent goes into toxic epidermal necrolysis, that is probably a very poor prognosis in dogs. We have tried to treat many patients with bills up to $10,000 and more and we able to reverse the condition after 7, 8 days hospitalization.
The wound healing is very slow and the infections are a big concern, specifically pseudomonas infections on the skin like in burn patients.
So sepsis is always an issue and the costs are just too high to keep them alive for this period of time. So I would always react very fast and try to suppress the reactions so they do not going to the higher extent. The higher the extent of body surface area eroded, the higher chances the patient may have a bad prognosis.
[00:20:37] Dr. Kelly St. Denis: Right. Okay, thank you. Yeah. That is just something that I found to be quite interesting when reading about how urgent that problem can be if it's advanced. So absolutely switching a little bit gears. I know we talked a little bit about plasma cell pododermatitis in the last episode, but I also wanted to talk about PNOE, which is proliferative necrotizing otitis externa, which is kind of an interesting problem that we don't see very often in cats. I've had a couple cases in my own career. They kind of can look like ear mites, a food allergy response, or at least that's. I've seen a few cases that respond to food changes. But what sets them apart in terms of the things that we see with PNOE that we wouldn't see with ear mites. I mean, obviously we're gonna do cytology to diagnose ear mites, but what are kind of the other things that we see in PNOE in cats?
[00:21:27] Frane Banovic: You know, I guess depends where you practice. Population wise, the vast majority of patients these days are getting some kind of an isooxazoline in cats. So therefore, the isooxazolines are very good medications that tend to deal with ear mites very efficiently.
So if you're suspecting ear mites with isooxazolines that I would say is relatively rare to see unless, you know, the owner is not really applying it and it just keeps tubes at home. The ear mites itself versus this disease.
So this disease, really, based on the images that we provided, causes these unique plaques.
So they are generally erythematous plaques. They are raised, bumpy, proliferative lesions. That's why they're called proliferative. And then they can have this hyperpigmented nature of these crusting on the top. I would say probably scaling with crusting the mites. And usually very uniquely, they tend to be preauricular, so before the entrance to the ear canal, although sometimes we see them in the ear canal as well. The mites itself, they don't like to usually cause any proliferative epidermal lesions like this entity. So just looking clinically, you probably would figure out, but just to be safe, you can always run your cytology Again, if you suspect you don't mites and you don't find them on cytology, doesn't mean they may not be there. You can still run your treatment therapeutic trial to be certain. It's this disease we really do not know a lot about. Proliferative, necrotizing otitis, it's called proliferative because, like I said, they tend to be like raised, elevated lesions. And it's necrotizing because there is a lot of cell death of keratinocytes in these lesions, likely associated with a lymphocytic attack.
Now, thinking about that, the most common reason why lymphocytes would kill epithelial cells, you would think infectious. So, like, if there is a herpes virus or if there is another virus, because, you know, usually to kill viruses, you send generally cytotoxic T cells. But many times when we stay in here or all the times that we have ever stained, we never find any virus. So we really don't understand the etiology of it. It does happen usually in younger cats, but can happen in older as well.
Usually tends to respond to immunomodulation. I would say it's 50, 50 with sometimes cats going in remission fully. And you can stop your immunosuppressors, but sometimes you may still need to do something that the lesions don't come back again. Really unique, unknown to us why this would happen once you see it. I think it's very unique. Clinically. Sure.
Yeah. Specifically, if you look at the images we show there, those are the classic examples of the disease.
[00:24:09] Dr. Kelly St. Denis: Yeah. And the patient that I had years ago had also a lot of skin lesions, which was interesting because they.
[00:24:15] Frane Banovic: Yes, they can do that too.
[00:24:16] Dr. Kelly St. Denis: And to be on the ears, but they can be elsewhere as well. So tacrolimus, I don't know if I'm saying that correctly. Is the preferred Tacrolimus. Thank you.
Is the preferred treatment then for As a topical.
[00:24:29] Frane Banovic: As a topical, yes. I mean people will use topical glucocorticoids depending what access you have. Tacrolimus is a. Is a calcineurin inhibitor like cyclosporine, except it's more potent and it's topical in why we use it in veterinary dermatology.
I think what probably usually happens is that, that people will use oral like oral glucocorticoids and a topical. You have to be careful that you apply it in areas that the cat cannot lick it off.
So groom it off. So absolutely. Like preauricular would be a good area because they cannot do that. So yeah, we will try to do tacrolimus but it's not wrong to do topical steroids either. They are just not ideal long term for the skin because they can cause skin atrophy, comedones and potentially even, you know, skin fragility. So you definitely don't want to use them forever.
Tacrolimus would be a better long term option if you can get that.
[00:25:24] Dr. Kelly St. Denis: Okay, thank you. That's much appreciated. I really appreciated the conversations we've been able to have. Like just really highlighting how practical these articles are for everyone. I really love how they're laid out in terms of each disease. How you have the pathophysiology, you know, signalment, how to diagnose and what are the clinical. Clinical features that are hallmark to those specific diseases and where to take your biopsies depending on the condition that might be suspected.
And so I just wanted to thank you again for agreeing to write the articles for us and doing such a great job and for joining us today as well.
Again we are talking about the Clinical Spotlight articles in the Journal of Feline Medicine and Surgery, Feline Immune Mediated skin disorders part two today, but we also have a part one that we discussed in our last podcast. So Dr. Banovic, again, thank you for joining us today.
[00:26:14] 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 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 the them with us by leaving a comment on our Facebook page or shoot us an email
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