So, welcome everybody. My name is Silvia Colombo and I'm from Italy, and I am a diplomat of the European College of Veterinary Dermatology. This afternoon, I will present 3 cases of immune-mediated skin diseases in cats.

Which are actually, managed with the immunomodulatory drugs. So it will be case-based, type of presentation, but we will also review some features and aspects of managing cases with immunomodulatory drugs. So case number one is Ricky.

Ricky is Devon Rex Scott. He is a neutered male, a young cat, 2 year old, and he weighs approximately 4 kg. Ricky was presented because of a severe pruritus and crust on the abdomen, and this problem was going on since approximately 3 months.

Ricky had been treated before by the referring veterinarian with the prednisolone at 1.25 milligrammes per kilogramme orally once daily in together with amoxicillin labulaic acid, and both drugs were continued for two weeks. The cut initially improved according to the owners, but then the situation got worse again.

When I saw Ricky, he had been on no treatment for 2 weeks. Ricky lives indoors, and is a single cat. There are no other pets.

Is regularly vaccinated and, the owners, as the majority of owners in Italy do when their cat is an indoor only one, is not on ectoparasite prevention. And it was fed commercial, dry and canned food. And also the owners were bathing Ricky once a week with a generic pet shampoo, thinking that the cat was actually dirty, and this is on top of the skin disease.

This is Ricky. You can see his, disease involves the whole, ventral part of the body. So ventral chest, abdomen, and, the axilla as well.

Ricky was already in anaesthesia when I took the pictures. If you look at the lesions more closely, you can see that these are actually, erythematous papules. Sometimes there is a little bit of, erosion on top of the papules.

And sometimes they are hyperpigmented. The lesions are also, coalescing and getting together to form larger, patches of hyperpigmentation. So, if we have to summarise Ricky's problems, we have a popular dermatitis.

We have erosive, primarily erosive, but as you know, you cannot really tell if a dermatitis is erosive or ulcerative based on the clinics only. You need histopath to be sure. So, normally, you talk about erosive ulcerative dermatitis.

There was also hyperpigmentation as a peculiar feature of this disease and also a severe pruritus, and the distribution was as said before axi ventral chest and abdomen. So I'm starting to think about differentials. I initially had a very long list, but just let me explain how this was put together.

Some diseases in this list are primary diseases, so I considered maculopapular cutaneous mastocytosis, which is also known. The dermatophytosis and demoticosis as primary diseases. Maculopaplar cutaneous mastocytosis is a bit controversial.

Some people think it's, it's a specific disease. Other people think that it could be a manifestation of allergies. So I put in the differentials or also.

The three most likely allergic diseases, so flea bite, hypersensitivity, food allergy, and environmental allergy. I also put an irritant or allergic contact dermatitis because the owners were shampooing the cat too often probably. Another primary possible differential is muscle tumour, and all these diseases can be Further complicated by a secondary superficial bioderma or malasthesia overgrowth.

So when we have such a long and complicated list of differentials, obviously, we need to start with the easy things. So we started our diagnostic workup with superficial skin skin scrapings, which were negative for mites and we ruled out the micosis. And also, we could not see fungal spores.

The dermatophytosis was also ruled out because the wood slump examination was negative, as well as the fungal culture. We took cytology of the eroded pupils, and we saw primarily neutrophils and xenophiles, which could go both with an allergic disease and with the urticaria pigmentosa like dermatitis. Haematology and biochemistry were within normal limits.

Ricky is a young cat, so we were not expecting anything, particular. It was done mainly because we needed to anaesthetize him and take biopsies. We did also serology for FIV and FELB and they were both negative.

And in the end of the first consultation, Ricky was given ihovacin, one injection at 8 milligrammes per kilogramme. To clear the lesions from any potential secondary infection and the biopsy was planned two weeks later. So, this is, these are the results of Ricky's histopathological examination.

In this slide, you can see the small magnification, small power images, and you can observe that there is quite a lot of hyperplasia. You see, this epidermis is thicker than it should be. There is hyperkeratosis on top, which is all this, purple.

Material up here. And you can also start to see that there is quite a lot of inflammation, diffused in the superficial dermis. The deeper dermis, the adnexa and the subcuti are not involved in the in the process.

So if you go on higher power, You can see here, there was a, a small, lesion, which is, was actually an ulcer, not an erosion, because the skin cannot be seen anymore. There is quite a lot of using enophilic debris up here, probably, something that was trying to become a crust. And also you can see, start to appreciate the inflammatory infiltrate, which was made of mast cells.

Let me find a nice example. Mast cells in cats look like fried eggs. That's what, what the pathologists say.

So this is a good one. And also by usingopils that were actually moving up towards the epidermis, at least in this in this area where the little ulcer was present. Higher power again, and you can see even better, a large number of muscles and a lot of einophis as well that were invading the dermis of this car.

So, the pathologist, actually made a diagnosis of maculopapular cutaneous mastocytosis, which, as I already said, is also, called, urticaria pigmentosa-like dermatitis. And another name that has been used over the years to describe this condition is xenophilic mastocytic papular dermatitis. All these names are because the first description tried to put together this disease to the human disease, which at that stage was called urticaria pigmentosa.

Then there was another group working on the disease that decided that it was better to stay, to stick with a more descriptive name, so it was called papular dermatitis with using infus and muscles. And the newest name is maculopapular cutaneous mastocytosis, because again, the most recent publication on this disease goes back to try to see if there are similarities between this disease and the human disease. So, in this paper that you can actually download because as far as I know, JFMS now is, is free to download.

So if everybody, anybody's interested can read the paper. Divided the cases in three groups, as, it happens in cutaneous mastocytosis in humans. They described a polymorphic form of the disease which was characterised by large papules, wheels on the head, neck, shoulder, and axilla, and this is a form of cutaneous mastocytosis in cats.

Ended up with spontaneous resolution in all cases. In the cases that had the, the more severe monomorphic pattern, there were a small crusted maculopapulus erythema, and this group of cats tended to progress to the chronic form of the disease, which is the pigmented maculopapular cutaneous mastocytosis. And this is characterised by chronic dermatitis, hyperpigmentation, and lichnification.

Examples of 3 cards with these 3 forms of maculopapular cutane mastocytosis to explain a little bit better. The polymorphic form is the less severe, and this is, I've seen it more on sphinx cats than on the Morex, and it's characterised by wheels, really, no, they are not pupils, they are just wheels that come and go and tend to be extremely erythematous. This form is the one that tends to resolve spontaneously.

As soon as the cat grows up, usually, it is a disease of younger cats. So, normally, at least the cases that I have seen with this, presentation tend to resolve spontaneously by 2 years of age. The monomorphic form is slightly more severe.

You can see in this nice example, erythematous papules. There is not a lot of hyperpigmentation here, not yet, but it, it will come. And also another feature of this disease, which may be present or not, sometimes the pupils are in line, as you can see here in this, in this image.

This was the abdomen of a demore affected by the disease. Third, the image is the most severe form, which is the pigmented maculopapular cutaneous mastocytosis, and this is also the most difficult to treat. It's, you can still appreciate some of the pupils.

There's quite a lot of, excoriations because this cut was extremely pleuric and had lesions, all over the body, but the more severe ones were around the face. So, where should we put Ricky, Ricky was probably something in between the monomorphic and the pigmented, and I am actually saying in between because these lesions were definitely more like the pigmented form than the monomorphic. But he did very well on treatment.

We initially started him on just on an antihistamine because this is the, one of the recommended treatments and if you're lucky and it works, it's a very mild type of treatment. It doesn't have adverse effects and the owners usually are very happy about this. So cetirizine at 5 milligrammes in total, so it's 5 mg per car orally once daily, and we also gave him some EAs, and this was the 1st 2 weeks while we were waiting for the results of the histopathology.

We also put him on monthly ectoparasite prevention with Luillanir because, as you remember, he was not on any prevention for parasites. So after we received the results of the histopathology confirming maculopapular cutaneous mastocytosis. We saw the cutback, and it did not improve on city.

It didn't respond, and that was not totally unexpected because, what they say in the paper, and also, it is also my experience, you get good results with And I mean, in the, the milder form. So in the one characterised by wheels, the polymorphic maculopapcular mastocytosis, the one that's in the end resolves spontaneously while you wait for the resolution, normally they do respond to syri. Then, so Ricky had to be treated slightly more aggressively.

So we put him on methylprednisolone, which is my favourite, glucocorticoid, and then I will explain why. At 2 milligrammes per kilogramme orally once daily. And we also schedule some telephone rechecks in order to be able to taper the steroids gradually.

We also advised the owner to bathe the cat less frequently, so we told them not more than every 2 weeks, and to use something very, very mild and very delicate, such as the other calm shampoo. So what happened, actually, Ricky responded very well. We saw him back two months after starting the glucocorticoids.

He was on 0.5 milligrammes per kilogramme once daily at that stage. So it was decided to try and reduce it to every other day.

And three months later, the cat was still in remission, so the glucocorticoids were actually discontinued. And the owner was also, we told also the owners to continue using the other kind of shampoo and not to bathe, Ricky more than every two weeks. And so it was lucky actually because probably together with the the Macular papular, cutaneous mastocytosis.

He also had, at least in part, he was irritated by the shampoo that they were using, we continue bathing. So it is also possible that he actually had two problems, one related to the shampooing and the other one to the primary disease. Cause normally, cuts at this stage do not, they do resolve completely, but then you cannot discontinue the treatment without relapses.

This is what happens in, in general, when they are the, in the chronic, pigmented type of, Cutaneous mastocytosis. So, just a few words on the treatment because we said that we were talking about immunomodulatory drugs. Sorry, I went back once forward one slide, forgive me.

So, the reason why I tend to prefer methylprednisolone is that it is, has less mineral cortico activity compared to the widely used prednisolone. And I don't know, I'm, I'm sure you have methylprednisolone in the UK, but as far as I remember, I did my residency in Edinburgh, so, I do remember that they tended to use prednisolone mostly. Because at that time, probably methylprednisolone was, was, only registered for humans.

We do have a 4 milligramme tablet called of methylprednisolone that we can easily use in cats. And it's much nicer than bread because, the owners will not phone you saying that the cat is drinking and peeing, all over the house. So definitely is, is a milder type of glucocorticoid in terms of adverse effects.

The dose has been established by the paper that I, I put, the reference up here. And the starting dose with methylprednisolone compared to Pred is 1.4 milligrammes per kilogramme orally once daily.

And the maintenance therapy, the dose should be 0.5 mg per gig orally every other day. So this is the indication that the authors give in this paper.

You go gradually from the attack dose to the maintenance dose. So actually, Ricky got a little bit more than this, but again, you need to Adapt to do this to the, the size of your animal. Tapering the dose is something that we do with glucocorticos and this, that is mainly done to reduce the adverse effects, but there is no evidence that you have to go every other day.

This is something that I learned from an expert on glucocorticoid therapy, who is Professor Ian Ramsey. And, we like the every other day, especially in, immuno-mediated diseases which pro require in the majority of cases, lifelong treatment with steroids. But there is no evidence that 0.5 every other day are better than 0.25 every day.

So there are no studies to prove this. The other, thing that owners ask me every time I, prescribe a glucocortico is should we use gastroprotectants. And actually, there is no evidence that they are needed and according to some publication, they actually may be also not good.

. They are recommended at the moment only if we are using very high doses of glucocorticoids such as for when we have to intervene in acutely, in, in acute cases of intervertebral disease. So if you need, if you have very high doses, if you need very high doses of glucocorticos, yes, you can do it. Otherwise, for the typical oral treatment with inflammatory or, or immune suppressive doses, you don't really need to add the gastroprotectants.

And the other thing that is very important to tell the owners is that even if the cat is on glucocorticoids, the cat needs to be vaccinated. Why? Because there is no evidence that being on glucocorticoids makes the vaccine dangerous.

There are no reports of, for example, I mean, vaccine virus react to reactivate because of the treatment that doesn't occur. And the worst thing that could happen in a cut on glucocorticoids that gets a vaccination is that the antibody response is not good enough. But, in this case, you can just maybe give another booster a few weeks later.

Nothing really, there is no contraindication in vaccinated, vaccinating cuts on glucocorticoids. And also this is true, as we will see later, also for other immune suppressive drugs because it's more dangerous to actually get the disease if you are on that kind of drugs then being vaccinated. So that's very important.

That you convince your owners to vaccinate their pets. And I think this is all for Ricky. And now I have my Screen blocked again.

Why? OK. OK.

Case number 2 is a cat called Rose Marino. Rosemarino is, I think, Rosemary in in, in English, but this was actually a boy. Rose Marino is a domestic short-haired, neutered male cat.

And he's a 6 year old of age. It was presented for crust on the face, on the ears, and on the pose. The this lesions appeared approximately 6 months before were slowly progressing and there was also moderate pruritus.

History of the Ros Marino. The first lesions appeared on the nose. And then, being enclosed and everything occurred within a month.

The referring vet thought about an allergic, a food allergy actually, so put the cat on a commercial hydrolyzed dry diet. Which the cat was eating since 4 months when I saw it. Is again an indoor only cat, who lives with two healthy cats, so the, cats living together and do not have any lesion and do not show ritus.

All the cats in this case were regularly vaccinated and on ectoparasite prevention. So images of Rose Marino, as you can see, there is a crusting, primarily, that's the lesion that you can appreciate more easily from the, the pictures. And this crust involve the nasal plane, the dorsal nose, and also are evident on the inner side of the pinna and the entrance of the ear canal.

And these are other images. So this is the other, ear on the other side. And you can see quite a lot of erythema and crusting.

And the lesions were also involving the outer side of the pena. So you see here that there is, again, quite a lot of crusting on both sides. It was very symmetrical, presentation.

Claw folds were also involved, as you can see, there was crusting around the claw, erythema and a little bit of whitish material could be expressed out of the claw fold. So again, summarising the problems, this is a primarily a crusting dermatitis. I put pustuar because after a very, very long search, I could actually find a few pastilles on the pin.

But, pusils and cats are very, very fragile lesions. So, in the majority of cases, you will not see, pustules, but just this, type of, yellow crusting. Under the, the crust, there is a rosy with erratic dermatitis, that you actually can appreciate if you remove the crusts, and there was mild pleats as well.

With the distribution, that we said before, it was on the dorsal nose, pin and nail folds and was very symmetrical as well. And this is very important, also the distribution of the disease. It is very important because very difficult that this could be an disease caused by parasites or something coming from the outside, because those diseases tend to be asymmetrical.

The only one exception is dermatophytosis that was on the list of differentials. You may have, may see cases of dermatophytosis in cats that are actually Must be differentiated by panficolios. They are actually identical in terms of, of clinical presentation.

It could also be an adverse drug reaction to something that the cat had before the onset of the disease because this is Always possible and also An adverse drug reaction could actually start painhigus foliacious. Drug-induced painhigus is reported, in both in dogs and in cats. Together with these three main differentials as usual, especially for the lesions around the, the nails.

We consider malaysia paraonicia or bacterial paraicia a secondary problems. So we started ruling out dermatophytosis and that was done with wood slump examination and fungal culture and both were negative. On cytology actually was not a difficult diagnosis in this case because we could see neutrophils and typical round basophilic Epithelial cells that are described as and called the cantolytic cells that are very numerous in diseases like in pan foliats.

We did bloods as well in this guts and we could actually find increased white blood cells, particularly neutrophils, and we did as usual serology for FIB and FELB and these were both negative. Again, we had to confirm the diagnosis with histopathology. So we started the cut on an antibiotic and in this case, we gave clindamycin.

At 11 milligrammes per kilogramme orally once daily, and a biopsy for histopathology was planned two weeks later. OK, so this is the histopath images of Rose Marino's skin. And I'll try to explain what you see in this image.

This is Small power image, but you can see that there was a huge pasture here, very big, with some crusting material on top. This is the, the roof of the pasture, which is made by the stratum corne of the skin, and this is the content of the pustule. Unfortunately, they got separated during fixation.

Within the past two, you see a lot of dark blue cells, very small, and some, more pink and larger cells. And these are the, the, a cantulytic cells that are very diagnostic when they Present in large numbers in cases of pain figures. It's not just the cantolytic cells that is important for the diagnosis, but also the size of the pus too that in pain figures, they tend to be very big, much bigger than what you expect in a bacterial infection.

I think we have, yes, we do have a closer view. So you see what is the content of the past too. You do have some Neutrophils, all these blue small, irregular cells are neutrophils.

And then you have all these round nucleated epithelial cells. In histopathology, they actually look more xenophilic than basophilic. The, the blue collar is more common on cytology, but still, you can see that these cells are actually Detaching from the the the underlying epidermis.

So this is a diagnostic for panhis foliations as the disease and the disease was actually involving also the wall of the follicles. This is a hair follicle and you see that the same cells are present at the entrance of the hair follicle. So, diagnosis confirmed, Rose Marino has 0figus foliages.

How do we treat this go? Let's start with a short summary on the more recent papers on the subject. There's been quite a lot of nice reviews recently.

One that I suggest you to read if you're interested is this one by Petra Visikova because again, it's free to download. And in this paper, she describes a group of cases of felinePF that she followed personally and she also did a big review of the existing literature. So it's quite a good paper to summarise the knowledge on this disease.

What happens in pain figures is that the immune system produces antibodies that attack the bridges between the cells of the skin. So you have one keratinocyte on this side, and another one on this side, and all this. Pro proteins, because actually they are proteins that connect one cell to the other, that all together form the desmosome, which is the structure that connects the cells.

And when these antibodies attack one of the proteins composing the desmosome, the two cells obviously detach from each other and by detaching, they tend to, they also tend to round up and this explains the Appearance of a cantolytic cells in when we do cytology. In humans, the protein of the desmosome that is primarily attacked by the antibodies is desmogle one. In dogs, it is desmocholine one, so it's a different protein.

In cats, we still don't know, we don't have a major antigen of panhious foliage, foliation known for cats, not yet. But recent studies actually showed that cats, the majority of cats with this disease have IgG, directed towards keratinocytes. It's just a matter of identifying the, the specific protein and we will get there probably in the next few years.

The disease has a very, very typical distribution, as I said, it's symmetrical and also tends to affect different parts of the body. You see in purple, the most commonly affected, which are the pina, both on the inner and on the outer side. Then less commonly we have the poles and the the claw folds, which is what our cat showed and also the nose, the both the nasal planum and the bridge of the nose.

Another peculiar location which is shown only by the cat, you don't see this in dogs is that sometimes you have pustuar lesions or, or crusts because of the reason I explained before, around the nipples. So, the nipple or the area around them is a very common location in in PF if it's, if your patient is a cat. When we have to treat these cats in general, it's a disease that it's considered to be less severe than its canine equivalent.

And this is because cats tend to respond better than dogs to therapy. In cats, therapy is in the majority of cases, and at least at the beginning, when we start treatment is based on only glucocorticoids. The suggested doses of prednisolone are 2 to 3 milligrammes per kilogramme orally once daily.

If the cut is not responding, you can go probably also a little bit higher. But recent studies have shown that you don't need to go that much high because they tend to respond pretty well. Remission time, takes normally 4 to 6 weeks.

And, we actually start with this high dose of glucocorticoids and we keep it until remission. So the first phase of the treatment is, daily, relatively high dose of steroids until remission, which means that we have no more active lesions. So you should not see.

Any more pustules, and also any more casting, . And then you start to reduce slowly your dose of leucocorticoids. In drug-related cases, there are, it has been reported spontaneous remission of the disease, so you stop the drug that is responsible of starting pan figures in your patient, and then the disease goes into remission spontaneously.

It's very uncommon, but it does occur sometimes. When you have to taper steroids, in, what it is suggested to do is to taper 25% of the dose every two weeks. And this, this is what I do as well when I start the treatment.

If I'm trying to control and relax, I go even more slowly than this. Trying to, because you need to try to identify the minimum effective dose in these patients. Sometimes you have to keep them on steroids and so it is important to identify which is the mini, minimum dose that will keep them without lesions and without uratus.

There are also cases that end up not very nicely and in the review article that I mentioned before, there was a 20% of death due to either the disease or the treatment, so adverse effects of treating pain figures. And death to disease is not because the disease kills the cat, but because maybe the owner doesn't like the adverse effects of the treatments or has problems in treating the cat. So basically, the, these cases are euthanized.

And in a minority of cases, it was reported to be about 14% of cases, it can actually end up discontinuing the therapy without relapses. So, in general, this disease has a better prognosis than it does in the, in the canine. What happens when you see adverse effects with your glucocorticoid therapy or when you see relapses while trying to reduce the dose.

Normally, what is done is to add a second drug. So you start with glucocorticoid monotherapy and then you add a second. Immunosuppressive drug, which can be in cuts in the majority of cases is cyclosporin or loambrus or chlorambucil trying to reduce the amount of steroids that this cat is receiving.

The most commonly used at the moment is obviously cyclosporin because it's registered and it's effective. The dose is, I found 5 to 10 mg per gig. I normally go with the recommended dose for allergies, which is 7 mg per kg or once daily, and I must say that they do very well.

Clorambuil is used is used currently less often because it's a human drug and because in, at least in my country, it is very difficult to, to find at the moment in pharmacies, and the dose in that case is 0.1 to 0.2 mix per gig orally once daily.

And one paper compared the results of the two combination treatments. So they had a group of cats treated with glucocorticoids plus cyclosporin, and a second group of cats treated by glucocorticoids and chlorambucil. And the results were actually much better in the end for the cats treated with the association with cyclosporin.

And they actually managed to completely discontinue the glucocorticoids in almost all the cats treated with cyclosporin and only in one cut out of 6 when the second drug was chlorambucil. Unfortunately, as usual in veterinary medicine, we have very small numbers, but, but it looks like cyclosporin is the best option. In some cases, you have a good control of the disease, but maybe there is focal area in which the disease is still active and instead of increasing the glucocortico, the glucocortico, it does.

Many clinicians prefer to add a topical, a topical treatment, which could be either a topical glucocorticoid or also tacrolimus. They both work. Problem with this kind of treatment is, as you expect, adverse effects, which is very common when you use glucocorticoids at, at these doses and also in this disease for a very long time.

The first one that is very common is to see recrudescence of, viral infections, especially herpesvirus and calicivirus. I must say that I see it extremely often. As soon as I start glucocorticoid, and doses, higher than 1 meat per gig, they start to sneeze and you have to, to treat, the recrudescence of, of the Erpes virus, particularly, together with your primary disease.

You also have, A lot of adverse effects related mainly to glucocorticoids, and they are listed in the slide, but I don't think I need to read all of them. You can read them, but also they, I'm sure that everybody is familiar with glucocorticoid adverse effects. The ones at the bottom are the adverse effects that you may expect if you use chlorambuil.

Chlorambuil is a little bit Like azathioprine in dogs, it tends to suppress the activity of the bone marrow. So you may see leukopenia, thrombocytopenia, anaemia, and also can cause increased liver enzymes. So what did we do with Rose Marino?

It was started at actually a relatively low dose of methylprednisolone. We started at 1.8 mg per gig orally once daily.

And then, we had, we saw him many times or we spoke to the owner on the phone because we actually were trying to reduce the dose as we, we said before. So it took approximately 6 weeks to get to the, complete resolution of the lesions. Rose Marino relaxed when he got to a dose of 1 milligramme per per kilogramme every other day.

We thought that more than that was not an acceptable long term. So we increased the methylprednisolone at 1 meat per gig once daily, orally, and we added cyclosporin and this needs to be done at the same time. Then we, once the disease was in remission again, we started to reduce glucocorticoids again and the maintenance doses for Rosemarino at the end of a, a long process of reducing gradually doses of these drugs.

At the moment, he's on methylprednisolone 0.5 me per gig orally every other day, and cyclosporin at the same dose, but every other day. So he gets one day, the methylprednisolone, and the next day he gets cyclosporin, and he's doing actually well.

So, we move directly to case 3. Case 3 is a complicated case, but also unfortunately, an unlucky case. I normally, try to, I don't really like presenting unlucky cases, but I also think that sometimes this is important because it's important to be aware of adverse effects of drugs and of, sometimes maybe mistakes by the vets.

Now in this case, probably I was not vigilant enough with this cat, but I'll tell you the story now. Mimi is an 8 year old, spayed female domestic short haired cat, and she is really a tiger, not a friendly cat at all. We could not even examine her without general anaesthesia because she was not nice to us.

And when she was, in the consulting room, she was also attacking the owner. So it was what we call a difficult patient. Line, the history of alopecia, symmetrical, to, to, to focal areas of alopecia on the flanks.

The whole story started 3 months before and according to the owner, the alopecia areas were increasing in size. There was not a lot of ris. Maybe the owner said that she was probably leaking those areas more often, but it was not something really.

Really bad and really continuous. The referring vet had treated her with antibiotics for 2 weeks without any change. Nene was an indoor only cat and she lived alone with no other pets.

She was living in, in an apartment and had access only to a small balcony. She was fed commercial dry and canned food based on chicken, and she was regularly vaccinated. I don't know how, probably, because I think they had to sedate this cat also for vaccinations.

So, on clinical examination in, on general anaesthesia, we did not find any particular abnormality in the general physical examination and there were, as I said, two areas of symmetrical focal alopecia with hyperpigmentation and erythema on the flanks. These areas actually were not just alupesic patches. They were palpable.

They were like very thin plaques. But if you, if you, if you touch those lesions, you could actually feel that the skin was thickened in the area of the lesions. So, I show you a picture.

This is, actually, we took the bioses straight away because we had already to anaesthetize the cat. So you see, this is one flank and this is the other. There was, alopecia, there was hyperpigmentation, and there was erythema.

And if you could lift the skin in a fold, you could actually palpate that there was something, in the deepest part of the epidermis and dermis. Well, within the skin anyway. So summarising Nini's problems were plaques on both flanks.

With my pitus and the disease was symmetrical, and at this stage, my differentials were, Not many, because knowing that that is not a flat lesion, but it's a plaque. Plaque means that there is something infiltrating the skin. So, the differentials were all related to diseases that actually infiltrate the skin.

So we consider that usingophilic plaque. Also feline lymphocytosis, cutaneous lymphoma, a muscle tumour, or feline progressive cytosis. Luckily enough, all these diseases are to be diagnosed with the biopsy and so we, we had to, as I said, to anaesthetize the cat to do the just the physical examination.

So we did everything in one go. We also did cytology, which was very interesting because on cytology, we could see, a, a monomorphic population actually. It was, the majority of cells were small, and basophilic, sustained in blue, with little cytoplasm, and it was the appearance of lymphocytes.

We did also, haematology and biochemistry. We did an abdominal ultrasound and we did thoracic radiographs. This was mainly to do a general checkup because of the personality of the cut, because no one actually ever did bloods on this patient before because of, I mean, she needed to be anaesthetized every time.

So we did also a general checkup. On histopathology, we actually confirmed a diagnosis of feline lymphocytosis, which is something different from lymphoma. In this case, you have a massive infiltration of small and mature lymphocytes.

These are not neoplasty. Plastic or abnormal cells are fully normal, appearing small lymphocytes that invade all the dermis and in the cat, they usually do not move through the epidermis. So it's known, it's called Well, it's I can't find the word anyway.

It spares the epidermis. It's just a, a disease that goes in the in the dermis and sometimes down deeper. Closer view, you can see that the vast majority of the cells, all the ones that are very dark blue coloured are small lymphocytes and you can also see that there are no lymphocytes in the pis.

So, the diagnosis for Nini actually was a suspicious, very suspicious for lymphocytosis. The pathologist suggested to do immunoisttochemistry for T cells, which is the CD3 marker, and B cells, which is the CD79A marker. And, immunochemistry was positive for this killingmphocytes, so for the CD3 marker.

And also the pathologist suggested to do the, the PA test, so PCR for antigen receptory arrangements which, which confirmed that that is the infiltrating lymphocytes were polyclonal, also the be but these were. Only visible in small aggregates. So, when you have a polyclonal population of neoplastic cells, it's not a tumour or in this case, it was confirmative of the diagnosis of the line lymphocytosis.

This is a disease that is, I would say uncommon, not really rare because you may, may see it. It's a lymphoroliferative disorder which is typical of older cats. It doesn't really, you don't really see it in cats probably younger.

Well, I've never seen it before 67 years old. As an acute onset, but it is characterised by, by a very, very slow progression. So lymphocytes, invade other areas progressively.

The lesions on the skin are very, very variable. You can have a lopecia like in this case, you can have plaques, you can have papules, erythema scaling, ulcers, crusting. It is very, very, Difficult to suspect actually before you do cytology because it could really appear as anything else.

This is another case. This lesion was, is on the inner side of the front limb and it really looks like and using ahilic plaque lesion to me at least. So it's very It's difficult because it mimics many other skin diseases.

The most common location according to published cases is the head and the neck, but, you can see lesions anywhere on the body. And the typical feature of the histopathology is full thickness perivascular to diffuse infiltration of lymphocytes, which are small to medium in size. They are mature lymphocytes.

Occasionally, you can have lymphocytes going towards the epidermis, and this is called, is described as epitheliotropism in 50% of the cases of lymphocytosis. Lymphocytes, as in Minne's case are normally CD3 positive and they are polyclonal. As I said before, it is a very slow disease.

When you diagnose it, it is almost always involving only the skin. It may progress to a systemic disease and involve lymph nodes or Abdominal organs and commonly at the diagnosis and slightly more commonly with the advancement of the disease. It could go on for years.

The survival is very long. It can be treated as, as you will see, we did it with Mini with the usual combination of glucocorticoids plus cyclosporin or chlora, you see. But the treatment, it usually does not resolve the disease.

You can have either a partial improvement or you can have a stable disease. So it, it, it doesn't move on to involve other locations on the skin or in the inner organs. As I said, long survival and also it has been reported, but I've never seen it, but it's been.

Reported that can progress to malignant lymphoma. So what did we do with Nini? We started her on the combination of methylprednisolone, to mix perkoralliances daily, and cyclosporin and the recommended dose of 7 mg per klis daily.

We had a resolution on one flank. So you see this, this is the right flank and the hair is growing back. And on the other side, the lesion was stable.

We managed to reduce the doses of drugs that Nini was, was taking 2.5 mg per kg of methylprednisolone orally every other day. While cyclosporin was kept at the same dose orally once daily.

And during 2 years, the cat was rechecked regularly with abdominal ultrasound, dermatology and biochemistry should probably have been done more often. My fault that there was also the problem of having to anaesthetize the cat every time we need to do anything, including just Dermatologic recheck. 2 years later, she came back with erythema and a little bit of scaling on the muzzle.

It was not really the nasal plane. It was more the skin around it and, and underneath. And here again, you could actually feel that it was a little bit thickened.

We did biopsies again and again, we had a diagnosis of feline lymphocytosis. So after 2 years, the disease had started to move to other skin sites. We brought back the methylprednisolone dose to 2 weeks per gig once daily, together with the cyclosporin, and then we gradually taper the dose again to maintenance dose.

After 1 year, so in total, 3 years after the diagnosis, the cat, presented to emergency with anorexia, weight loss, vomiting, and, PUPD. The lymph lymphocytosis at that stage was stable. There was no improvement and no worsening, and she was on maintenance treatment.

Initially, we thought that we either induced diabetes mainly with the glucocorticoids, or we thought that maybe the lymphocytosis is actually progressed to multisy lymphoma. We did some bloods, again. OK.

We did bloods on Mini. Nini had High blood glucose, but not terribly high and normal lutozamine so it was not really consistent with diabetes. She, she had a low albumin globulin ratio, but generally again, also the, the blood proteins were not very high, albumins especially, and she, she had, she was anaemic, very low haemoglobin and low hematocrit.

So she was actually not feeling well and also the exams were not particularly good, but we initially did not find anything specific in the blood tests. So we went on and Minne underwent abdominal ultrasound. And in this exam, the echographist observed enlarged celiac and mesenteric lymph nodes.

Ymph nodes were aspirated andological examination showed a very uncommon Problem which is actually mycobacteriosis. So what happened is that due to the immune depressing, immune depressive treatments that Mini was undergoing, she got infected with mycobacterium. Mycobacteria are difficult to see on cytology because they do not stain, with the normal, deep quick type stains that we use for cytology.

They require special stains, but they can actually be appreciated as a negative image. So the mycobacteria within these cells, which are all macrophages, are the white. Short lines that you can see if you look very closely.

Another image in which you can again see this sort of white little sticks which are the mycobacteria. Mimi was at this stage was euthanized and underwent microupcy, and the final diagnosis was unfortunately, intestinal microbacteriosis caused by mycobacterium avion complex. Why identifying the specific mycobacterium is important.

It is because it is probably the only one that an indoor cat can easily get. And this is because, at least in my country, the majority of indoor cats, have access to balconies, and we have quite a lot of birds flying around, especially in big cities. This cat lived in Milan, where we have a lot of pigeons.

So it is possible that the cat got infected through, pigeon pigeons droppings, for example. Mycobacteria in general are intracellular acid fast glow, slow-growing bacteria. They live inside the macrophages, and they are grossly divided into three groups.

There is the group causing tuberculosis, which is composed by mycobacterium tuberculosis, bovis, and the newly reported microti, and this tend to give a systemic disease. There is one single species of mycobacteria that causes leprosy in cats, and that's mycobacterium leprimorium, very rare as well. More commonly reported are the non-tuberculos group.

And again, we have some mycobacteria that tend to be very slow growing on culture media and some that are defined rapidly growing. Probably the rapidly growing ones are the most common that we may identify and among the rapidly growing, mycobacteria, we find the mycobacterium complex a complex. And this is, as I said, the most common one, at least in Italy, and it is a mycobacterium that can give you both cutaneous and systemic disease.

It's normally Got comes from the environment and can affect birds, humans, dogs and cats. Generally speaking, mycobacteria cause granulomatous to biogranulomatous inflammation. Abium particularly is tends to go more commonly systemic than in the skin.

And when, when it is a systemic infection, the most common locations are the respiratory tract or the digestive system. The signs that you may notice clinically are very specific because you see the cat that stops eating, loses weight, and you can feel increased size mesenteric lymph nodes. And the diagnosis usually requires ultrasound and cytology, like in this case, or a biopsy, on histology, you need the, the yin and acid-fast special stain to identify mycobacteria.

PCR is useful if you want to identify exactly which species are you looking at. Generally speaking, the infection by mycobacterium abium is a very poor prognosis. And unfortunately for, for me, it is typical of FID FELD infected cats, but also of cats on glucocorticose and cyclosporin.

So as I said at the beginning, probably my fault, I should have looked more closely at this cat. But on the other hand, with the problem of needing sedation, every time we had to recheck the cut, the exams and, and all the monitoring was probably a little bit, well, not probably, was delayed, should have been rejected every 3 to 6 months and not every 6 to 8 sometimes. But such is life and it's a case that is not with a happy end, but I want you to present it because it's very important to be aware that we can actually have this kind of problem when we use immunosuppressive drugs.

And with this, I think I'm no, I just a few words more on cyclosporin that I want to finish off with. Also, when you use cyclosporin, it is recommended that the cat is tested for FIV and FELV. When cyclosporin came on the market, it was also suggested to test for toxoplasmosis.

Which is not recommended anymore, but it's important that the cat is kept indoor, so it's not allowed to, go hunting, and that the owner does not feed the raw meat, because that's the easiest way to contract toxoplasmosis. Cyclosporin needs to be given, according to the manufacturer on an empty stomach, but on the other hand, it can cause nausea and vomiting in many cats. So I normally suggest the owners to start on a full stomach, and then if the cat can tolerate the the drug and takes it without problems, then move to, towards the empty stomach administration.

As said before for glucocorticoids, these cuts on cyclosporin must be vaccinated because for the same reason that I explained before, there is no reactivation of vaccinal viruses, but it's very dangerous for immunosuppressed cats to contract the virus disease because With this kind of treatment going on, any viral disease could probably kill the cat, as it happened with mycobacteria in this specific case. Other adverse effects reported for cyclosporin, together with the GI said are weight loss. So you need to check the weight of your, of your cats on a regular basis.

You may see gingivalarperplasia, although less commonly compared to dogs. And also, in this case, you can have reactivation of ocular or upper respiratory viral infection. As we said before, reactivation of herpes virus is not uncommon.

And another peculiar adverse effect which is seen only in cats is the acute, this should be sorry, that's a typo. It is acute bulu keratopathy. This is an eye disease which is seen, it's an adverse effect of cyclosporin.

Also, when you use cyclosporin, be aware of drug interactions. So if the patient is taking other drugs, other than, cyclosporin and maybe glucocorticos, make sure that you check if there is any interaction with other, other treatments because this could, again increase a lot, for example, the concentration of cyclosporin in blood and you can then have serious problems of overdose. So, having said that, I'm done with this presentation.

I really hope you found it interesting and also entertaining. And if you have any questions, just feel free to, to ask. Thank you very much.