OK, thank you very much and welcome everyone to tonight's webinar. Which is on the topic of dermatological manifestations of internal disease in both dogs and cats. So the skin's appearance and its health is influenced by many things which we're all aware of, and I guess a lot of the things we think of are external things such as parasites, potentially environmental factors like allergens, but also overgrowth of surface micro microbes causing infections.

But tonight's talk is all about internal factors that might influence the appearance and health of the skin. And the skin and the changes that we see with the skin can be markers of internal disease. And one of the beautiful things about the skin is that it's so superficial, so the changes are often noticed by owners and can be some of the first things that are noticed by owners.

Now some of these things that we're going to discuss tonight could be linked to one particular organ or they might be due to multi-systemic disease. But the purpose of tonight's talk is to try and give you a bit of an overview so that you'll become more familiar with some of these characteristic skin presentations linked to internal disease. And some of these can be very characteristic.

And I'm certainly not going to necessarily say they're all common, but some of them are very characteristic. So if you can become familiar with at least remembering what they look like, then it'll least be a good guide to how to investigate these sorts of things when they crop up. So there's different ways of trying to group these diseases, but we see skin disease associated with hormonal changes.

We have the groups, the group of paraoplastic diseases, and then we have skin disease associated with nutritional and metabolic changes, and it's these three groups that we're going to talk about mainly tonight. There are also systemic infectious diseases that can cause skin changes and also systemic autoimmune diseases, but we actually don't really have time to talk through those in this hour talk tonight. Some of the infectious diseases could include things like Lichmania, potentially systemic fungal infections like cryptococcosis, sporotrichosis porotrichosis which we see from time to time.

Potentially viral diseases, maybe like distemper and herpes virus, but you could pretty much do a talk just on that topic, and, and, and that could easily last an hour, so that needs to be done on another day. Equally, we don't really have time to cover the autoimmune diseases such as systemic lupus erythematosis, and erythema multiforme, for example. But we're gonna focus on the three, groups that I mentioned to start with.

So we're gonna start off with the hormonal changes. Now the endocrine diseases are very good examples of the link between the skin and internal disease. And these three diseases, hypothyroidism, hyperadrenocorticism, and sex hormone imbalance are the most important ones to be aware of.

And we're actually gonna mention sex hormone imbalance, which really when we're talk, when we say that we're talking about hyper estrogenism, we're gonna actually mention that as part of the paraplastic diseases because that can be associated with testicular neoplasia. But we're gonna start off with hypothyroidism. Now thyroid hormones, as I'm sure you're all aware, have a huge number of functions, but when thinking about the skin, they have a numerous functions as well.

And one of the main things they do is that they stimulate allogen, which is the growth phase of the hair cycle. So one of the problems of not having enough thyroid hormone is that we have poor regrowth of hair, and we don't really get that normal cycling through the hair cycle. As a result, hairs go through the hair cycle and then just don't start growing again, so we end up with non-pytic alopecia.

And one of the things that owners will often report is that we get poor regrowth after clipping. Now this picture shows you a dog that is hypothyroid, and you can see that we've got alopecia around the neck. And that's really just because.

That's an area that's being rubbed and these hairs that are in teelagen and not going through into antigen properly just get easily rubbed out. Thyroid hormones are also important in the process of quantification, so we will see scaling and hyperpigmentation, sometimes a dry and dull coat, with hypothyroidism. We also see dermal changes, and hypothyroidism causes accumulation of glycose aminoglycans in the dermis.

And that leads to this mix edoema, which you'll probably all be familiar with from reading the textbooks can lead to this tragic facial expression of dogs because of this deposition of glycosamminoglycans in the dermis. Thyroid hormones are also important for the epidermal barrier integrity, and hypothyroid dogs are predisposed to recurrent skin and ear infections. In fact, hypothyroidism is actually one of the recognised primary causes of canine otitis externma.

So this is a hypothyroid dog, a before and after picture, quite dramatic, I'm sure you'll all agree. This is a West Highland white terrier, that we saw at my hospital. This dog had atopic dermatitis and concurrent hypothyroidism.

Now on the left here, this dog's obviously extremely alopeciic and and and more alopeciic than you'd typically expect for an atopic dog. But. As you can see, by adequately supplementing, the dogs, with thyroid hormone and managing the dog's atopic dermatitis, he went on to do very well.

Now this is a quite an old picture. This is the best example that I've got to try and demonstrate this tragic facial expression of the glycosamine and glycans and the myxedema, in this in this dog and and that can be seen with hypothyroidism. I think it's sometimes something that's quite difficult to pick up on, but, but this is the best example that I've got.

Now moving on to hyperadrenocorticism. So this can occur as a naturally occurring disease, but it can also be due to iatrogenic hypercortisolism. Glucocorticoids have lots of effects on the skin.

And they certainly have effects on the process of quantification. And dogs with HAC can suffer from scaling and comodomes which are blackheads. And HAC also increases the chances of secondary infection, and these dogs are predisposed to adult onset demiticosis.

So certainly when we see demidiosis in an adult dog, we need to be looking for underlying causes such as this. Glucocorticoids have effects on the fibroblasts, inhibitory effects, that is. And that has effects on collagen production.

Leading to dermal thinning, delayed wound healing, thin hypotonic skin. And these dogs bruise quite easily and because of the very thin skin, you can often see the dermal blood vessels very prominently through the surface layers of the skin. They have negative effects on hair growth, and they cause yo sebaceous atrophy.

That obviously leads to the classic bilateral symmetric alopecia that we associate with hypogenic corticism. It also leads to a dry, dull hair coat, just like hypothyroidism, and it can lead to lightening of the hair coat as well. And it's thought that might well occur because hairs are being retained in the vesting stage, teenaging stage, and there could be an element of environmental bleaching.

But the reason we get this alopecia is cos glucocorticoids have an inhibitory effect on allergens, so they prevent that orderly progression through the hair cycle in a similar sort of way to it happens in hypothyroidism. So this is a picture of a dog with hypogeniacorticism. I'm sure you're very familiar with seeing these sorts of dogs, but this dog demonstrates the pot-bellied appearance from the atrophic effects on the muscles.

And this dog had actually been clipped some time previously for an abdominal ultrasound examination and quite nicely demonstrates poor bee growth of that area after clipping. This is another example. This dog doesn't really look so pot-bellied, but hopefully you can all appreciate there is quite extensive, visually non-inflamed, truncal alopecia, on this dog.

And also, particularly you can see just over the dorsal neck, the skin looks very hyperpigmented, and quite sore. And that's actually, progression to calcinosis cutis at that site, which we're gonna talk about in just a moment. So calcinosis cutis is something that I thought it's worth mentioning because that certainly can be linked to hypoadrenal corticism.

It can form due to dystrophic and metastatic forms. Dystrophic calcification occurs secondary to either naturally occurring hypoadrenocorticism or iatrogenic hyperglucocorticoidism. And certainly I've seen calcinosiscuis develop in quite a lot of dogs when they've been receiving daily steroids for various conditions, but sometimes when they've been given daily steroids for the control of immune mediated diseases, and I'll show you an example in a moment of a quite a dramatic dog that had been taking daily steroids.

Some dogs are much more sensitive to the effects of steroids than others, and a dog that might be on a very high dose might never develop calcinosis, whereas another dog that's much more sensitive might develop it on really quite low doses. And really the pathogenesis and reasons this forms is quite poorly understood. It does cause quite characteristic skin lesions though, which is why I thought it was worth mentioning and discussing er this evening.

Initially, calcius is acute it often develops as just erythematous, macules and papules. But over time, these papules become take on a rather hard and gritty appearance, often coalescing into plaques. Prris can be present, but it's probably more often present when there's secondary microbial infection, which these dogs are certainly er predisposed to.

And calcinosis cuis often develops in areas with chronic flexible movement, so classic locations would include the dorsal neck, which is like the picture I just showed you then, the axillae, inguinal areas, and can also sometimes occur in areas like the mucous membranes and in the mouth on the tongue. And these lesions can can become quite dramatic and they can bleed and ulcerate and then secondary infection is then very, very common. Metastatic forms of calcinosis cutis will generally occur in animals with renal failure, so they're quite, quite different, forms of, of the dystrophic forms which are either due to naturally occurring hypogeniacorticism or iatrogenic hyperglucocor.

So here's some pictures. So this is a dog, this is over the dorsal sort of scapular area of a dog, and hopefully you can just about make out that we've got erythematous, papules and plaques in amongst this area of thinning hair. And I think sometimes photos don't quite do this justice because you really need to actually feel these lesions to really get a sense of how hard and gritty they are.

Really not much else can really feel like this, and certainly if you see this type of le. In a characteristic location like the dorsal neck, then you really need to be thinking about whether this dog is taking steroids or whether it may be producing too much of its own steroids, or, or potentially whether there may be signs of things like renal failure. Here's an even more dramatic example.

Similar lesions though, hopefully you can appreciate we've got erythematous papules almost progressing to nodules in this particular dog, becoming, you know, quite large lesions, but extending along most of the trunk on both sides. And then this is the dog that I alluded to earlier. This is a dog that was taking daily steroids for quite some time for a steroid responsive meningitis.

And hopefully you can see that and appreciate that this dog had really quite an awful area of dermatitis over the dorsal neck, which really, you know, the owners quite understandably were quite distressed by this particular situation, and, and actually this picture doesn't really do it justice because this dog had much milder lesions going along the entire dorsum. And the after picture, this, this dog is just after getting this dog off daily steroids and onto another immunosuppressive dosing regime, and you can see that this dog did have lesions going along the whole chunk, but you can see that the prognosis can be quite good for these dogs, especially if the underlying trigger can be addressed and corrected. It's more difficult, in a poorly controlled, natural, naturally occurring hyperrealcorticism case.

Some of those cases can be very, very difficult to control, and, in some cases it can be almost impossible to keep on top of secondary infection. In some cases, osseous metaplasia can occur, and if osteomacutis forms, well, that really isn't going to resolve. So those are the sorts of cases where the prognosis for a resolution of the skin changes can be very poor.

OK, now moving on to another interesting and quite dramatic condition. This is acquired skin fragility syndrome, which I also just mention at this point because of the links to hyperadrenocorticism. This occurs in cats, and it has been associated with hypoadrenal corticism and particularly those that those cases associated with adrenal tumours.

It has also been linked and associated with iatrogenic hypodgenic corticism, but also with the excessive levels of progestational compounds, either from the adrenal tumours or administered products. And then in rare case reports, it's been linked to hepatic lipiddosis and neoplastic conditions as well. So, generally it's thought that.

The the skin syndrome that we see is due to the atrophic effects of these disorders or the drugs on the skin. Now this is a really quite a horrible condition because cats develop very thin and fragile skin. Now this is quite different from something like Ehlers-Danlos syndrome, which you may have heard about, which is the genetic disorder of collagen where animals can develop stretchy skin.

So animals with acquired skin fragility are not, they don't have stretchy skin, they just have really thin skin that tears easily. So in these cats, even just gentle touching of the skin can really rip the skin open and cause really quite awful gaping wounds. And certainly once you've seen a cat with this sort of problem, you don't really forget it because it really is quite an unpleasant thing to see.

The best way I can describe it is almost like the skin is so thin, it's almost like wet tissue paper. So here's an example of this, so, these cats really just even by touching them like I said, and certainly with a cat, scratching at the skin can really cause quite awful lesions in a very short space of time, and, the skin just often peels away just from being so thin. So if you were to see this sort of thing in a cat, and it's sometimes, and certainly in the cases I've seen tends to occur over the sort of dorsal and dorsal neck, it should prompt a search for hyperadrenal corticism in these cats, and blood testing and abdominal imaging to look for an underlying trigger.

I hope you don't see this very often because it's not nice. And certainly if we can't identify an underlying trigger for this, then the prognosis can be very poor, but usually if you can, address the underlying cause and and manage these wounds as best as possible, then some of these can, can do OK. OK, moving on to the pooplastic er diseases.

So these are skin disorders that result from internal neoplastic disease. And by definition, by removing the trigger, the skin disease should resolve in these cases. That's, that is the general definition, but it's always quite difficult to obtain in practise because removing the trigger is not always very easy in some of these diseases because the trigger can be quite an unpleasant and severe cancerous condition, so it's not always possible.

So the first one to discuss is feminization associated with testicular neoplasia. And this links in with the skin changes associated with hyper estrogenism. Now in the majority of the cases, it is presumed to be due to hyper estrogenism.

And that's because most of these testicular tumours have been found to be sattoni cell tumours, and these are oestrogen secreting. But it is just worth mentioning that the jury is still slightly out because some studies have shown elevated oestrogen, while others have not. Some have demonstrated increases in in sort of oestrogen intermediates, and some have shown that there might be a shift in the sort of oestrogen to testosterone ratio.

But it is always quite difficult to interpret the results of some of these tests because hormonal concentrations do fluctuate. What is known is that certainly we can see the presentation of feminization and skin changes also occurring with semenomas and interstitial cell tumours of the testicles. Feminization of syndrome occurs in about 24 to 57% of dogs bearingsodi cell tumours, so certainly not all of them.

And these tumours themselves are normally fairly asymptomatic, so owners are not necessarily gonna notice these things, it's normally going to be the secondary changes associated with them that that they will notice. And satto cell tumours do have a low metastatic potential on the whole. So dogs that develop these testicular tumours can have skin changes associated with this presentation.

They can develop feminization, or both, and we'll talk about the clinical signs of these now. So the syndrome of feminization includes this list of clinical signs, so pendulous prep use, gynecomastia, which is the development of the mammary guns in a male dog, penile atrophy. We can see bone marrow suppression and aplastic anaemia due to the hyper estrogenism.

Some of these dogs will display behavioural changes and attraction of other male dogs. There are a number of skin changes to be to to be aware of that are linked to testicular neoplasia. Now oestrogen inhibits allergen of the hair cycles.

That's similar to glucocorticoids with dogs with HAC. So if it's inhibiting allergen, those hairs aren't going to go through orderly through the hair cycle, and we're then going to lead, it's going to lead to bilateral symmetric non-ptic alopecia. These dogs will also develop hyperpigmentation, and one of the really interesting clinical signs we sometimes see is macular melanosis.

Macular melanosis means flat excess pigmentation, and, and that tends to form in the around the genitals of these dogs. So an increase of flat areas of pigmentation in and around the genitals is reported to be suspicious for dogs with testicular neoplasia producing excess oestrogen. Another very interesting clinical sign is this linear prepetial dermatosis.

This is where dogs with these testicular neoplasms develop pigmentation changes that extend from the prepetial orifice along the ventral surface of the prepuse down to the scrotums. It's a band of pigmentation change along the bottom, basically on the, along the ventrum ventral surface of the prepus. And that's actually reportedly a fairly pathognomonic clinical sign for dogs with testicular neoplasms.

So it is pretty rare and unfortunately I haven't got a nice picture to show you of that because I, I don't, I don't see this very often, but certainly if you were to see that band of pigmentation along that along the pet piece, then I definitely would be wanting to investigate whether that dog had a a testicular neoplasm. How do we diagnose feminization? Well, clinical findings and histological evaluation of the testicles to confirm a tumour, and then ultimately a response to castration, which should then lead to improvement and resolution of the signs of feminization and resolution of the skin changes if they are present as well.

So here's a picture. This is a dog that had hypoestrogenism as associated with testicular neoplasia. Now this dog doesn't really look any different from that dog that I showed you at the start with hypothyroidism.

It's got a visually non-inflammatory alopecia around the neck, which is an area that's getting rubbed from the collar. These hairs are easily going to be rubbed out because they're in tealagen and not growing properly. But the, the important point really is that the alopecia associated with hypothyroidism, hyperadrenal corticism, and, sex hormone imbalance or hyper estrogenism can really look the same.

OK, moving on to feline perineoplastic alopecia now, this is a very distinctive presentation er linked to internal disease. So if you can remember this one, it's definitely worthwhile. So this is an alopecia condition of cats associated with internal malignancy.

And it's been most often linked to pancreatic adenocarcinoma. But there are other tumours that have been mentioned in case reports and I, I'll put you a list here. So numerous other tumours of the liver, even the colon, but certainly the pancreas is the organ that has been most associated with this skin presentation.

And a path a mechanism by which the skin signs occur isn't really known. But the skin changes are usually one of the first things to be noticed by the owner. Usually affects older cats, but there are no breed predispositions.

And this alopecia condition presents with bilaterally symmetric progressive alopecia. That often has a ventral distribution, so that's quite unusual, it's quite different from other alopecia conditions. So it often starts on the ventral trunk and extending down the abdomen and then extending down the limbs.

And the real classic hallmark of this particular syndrome is that the skin takes on a really shiny, almost glistening wet appearance, which you really don't see with any other alopecia condition. The foot pads can also take on a rather dry, scaly appearance. And some of these cats can then develop secondary malathcasia infections.

Now malascasia infections, especially if they're generalised in cats, are quite unusual, and it's always quite a worrying sign to find that because it tends to suggest that this, the cat in question has some sort of systemic disease process occurring, so it's never really a good thing to find. And and it's also just worth mentioning that this, the skin is very shiny in this, these cases, but it's not fragile, so it's quite different from the skin fragility syndrome cats with the ripping that I mentioned a bit earlier. Now these cats will also often be unwell, and that's because of the underlying disease process.

So you, you may have them presenting with weight loss, and they could be anorexic, they may have vomiting or diarrhoea, and they may be lethargic. But it, but it might actually just be the skin signs that are initially the the owner's main concern. Histopathology from this alopeciic shiny skin demonstrates epidermal hyperplasia, which actually shows that the epidermis is actually thicker than normal.

But it does demonstrate marked follicular and adnexial atrophy, so . So the, the follicles are getting smaller, miniaturisation, and they're they're generally in teelagen, so follicular tagization, they're not going through the normal cycling. And then we also tend to see thinning or absence of the stratum corneum, so even though the epidermiss shows hypoplastic change, the absence of the stratum corneum is probably the reason why we have this gross appearance of the shiny glistening skin.

So this is probably the best example that I've got to show you. It is a relatively rare presentation, but this is an older cat, I think this cat was about 15, and lifting up the cat, you can see underneath on the right, this picture on the right demonstrates this cat is just very alopeciic. It's just the picture just doesn't quite do it justice to demonstrate the shiny appearance, I'm afraid.

But hopefully you can appreciate that it is visually non-inflamed. This cat is not heretic, it's not groomed this hair out itself. These hair follicles are just atrophied and miniaturised, and classically, as I said, this skin would have a rather shiny appearance.

And if you're to see that, you, you need to go looking for internal disease. This is the same cat's claws, and hopefully you can just about make out you've got little brownie black waxy deposits in the inter digital areas of this cat which were present all around the claws and on all four paws, and surface cytology from this exudate demonstrated abundant malacasia yeast. So that was incompatible with this dog having a systemic disease process.

So recognising this shiny skin presentation should prompt imaging of the abdomen. You might also consider performing chest radiographs to look for signs of disease spread. Ultimately you'd need to perform surgery to obtain a tissue biopsy to confirm the diagnosis of neoplasia.

But the prognosis for cats with this problem is often quite poor because many of the underlying neoplastic conditions metastasize quite early on. And in one report, 12 of 14 cats died or were put to sleep within 8 weeks of the onset of the presentation. So this is not really, this is obviously a very unpleasant presentation to diagnose, and it has very important implications for the cat, but it is important to be able to recognise it because really not many other things, or no other presentation will cause this ventral distribution of shiny non-poietic alopecia.

OK, so another paraneoplastic syndrome that we need to be aware of is feline thymoma associated exfolio of dermatitis. And this is another rare skin disease, so I'm certainly not suggesting you're going to see this on a weekly or monthly basis in practise. But it's been associated with thymoma.

Although the actual underlying pathogenesis is not not really known, it's thought to be immunological, partly because there are some similarities with the disease erythema multiforme. It might be a a sort of anti-tumor response that leads to autoantibodies, or it might be that the tumour is producing a substance then triggers the disease. Skin lesions generally start on the head and the pinny with scaling.

And then over time they then generalise erythemur and scaling sort of then extend further over the whole body. Erosions may develop over time, and it's these cats are usually non-chloritic, but secondary infections are quite common. And certainly when they happen then pruritus can occur.

Some of these cats will be unwell, so you could have relatively vague clinical signs such as lethargy, anorexia and weight loss. And some cats may present with respiratory signs due to the intrathoracic disease present. But it is possible that these cats could just present with skin changes noticed first of all.

So it's important to be aware of cats with expoliative dermatitis, so widespread scaling dermatitis could have this presentation and could have a thymoma underlying this. Histopathology, taking skin biopsies, well, that would demonstrate a cell poor hydropic interface dermatitis with apoptosis, which is quite like erythema multiforme, so it suggests an immunological mechanism. There is mild to marked ortho keratotic hyperkeratosis, and it's that that leads to the widespread and dramatic scaling that we see grossly on these cats.

Here's just an example of a cat with exfoliated dermatitis, hopefully you can see that this cat over an entire body surface pretty much has very marked and quite thick scaling, which is so thick in places that we're actually forming linear cracks and fissures in the skin. So you can imagine that this within those areas, a secondary microbial infection, would be, would be quite quite common. Other potential differentials for this sort of presentation would include things like drug eruption, potentially contact dermatitis, but that would be quite rare.

You could have other immune-mediated diseases like systemic lupus rohematosis, potentially pemphigus foliage or although that is more of a, postular crusting dermatosis. And certainly you'd need to be looking for concurrent fungal and yeast, and bacterial infections, that might, be causing or contributing to this. So recognising this presentation should prompt imaging of the chest looking for that thymoma.

If something is seen, then it would be normal to attempt transthoracic and needle aspirates and potentially needle core biopsies to try and get a diagnosis. Removal of the thymoma will and should lead to resolution of the cutaneous signs in keeping with the definition of a paraneoplastic syndrome. The resolution of the er skin signs can take several months.

And It does depend a little bit on the individual case and the thymo question as to how easy it is to try and sort, sort it out. If the thymoma is non-invasive and resectable, the prognosis should be relatively good, but some thymoma can be very invasive, and in those cats, the prognosis can be really quite poor and they often don't really survive the perioperative period. I just also thought it was worth mentioning that Monica Linek in a few years ago now published an article demonstrating that this reaction pattern of exfoliative dermatitis in cats can in some cases be an idiopathic finding.

They certainly in these cats, in these cats looked for thymoma and didn't find anything. So in those, in those rare cases where you don't find an underlying trigger, then those are usually going to need immunosuppressive treatment to try and reduce the inflammation that's occurring in the skin. If the farm owners are non-invasive and resectable.

Then the prognosis should be pretty good, as I said, and actually the median survival time is is almost 2 years in, in these cats. Now I also just wanted to quickly mention that this is a very, very recent report. In fact, this is, this is an article that's just literally come out this month in the veterinary dermatology journal, which described a report of thymoma triggering paraplastic alopecia.

So rather than triggering the exponative dermatitis that I've just been talking about, this case, the cat developed a paraplastic alopecia, which, as we've just discussed, is more typically seen associated with pancreatic and hepatic tumours. But this cat still developed the multifocal non-inflammatory alopecia with a shiny appearance. So it's important just to be aware that not every animal is always going to read the textbook perfectly, but if we see these sorts of skin reaction patterns, it's still important to go looking for a neoplastic trigger, but it might not necessarily be one that perfectly fits the textbook description.

Right, moving on to nodular dermatofibrosis, so that there is some debate surrounding this condition which we'll talk about in a minute. But historically, this has been described as the development of nodular dermatofibrosis and nodular skin lesions in association with renal cyst, adenocarcinomas or cyst adenomas. And it's been most often described in German shepherd dogs and their crosses.

Usually when they reach middle age and there's no sex predilection. Skin signs develop or present with nodules usually on the limbs, which are non-poritic and usually in the dermis and subcutis, so they're not really, they're not involving epidermis, they're sort of under the skin. Over time, renal signs develop, which are slowly progressive and often bilateral.

There've also been some cases reported with uterine liomyomas in females, although the clinical relevance of this finding is a little bit uncertain. And biopsies of the skin shows dense collaginous hyperplasia. So I appreciate seeing nodules in the skin.

You wouldn't necessarily think this dog's definitely got nodular dermatofibrosis, but certainly if you were to take biopsies of those nodules and get that report back with coaginous hyperplasia, it should prompt you to start thinking, well, is this a German shepherd dog? Is this dog middle aged? Could this dog have other signs such as renal disease that we need to go investigating?

So recognition of this problem should then prompt ultrasound of the abdomen. Potentially females should be spayed if there's uterine yomas that have been identified. But certainly renal functioning, a function monitoring needs to be on the agenda.

And actually renal biopsy would really be needed for confirmation of the of the underlying neoplasia. The problem with this syndrome of nodular dermatofibrosis is that there's no effective treatment. Because this condition normally affects both kidneys, nephrectomy is really rarely an option, and it is slowly progressive, so these animals will eventually develop renal failure associated with this syndrome, which is obviously, you know, not a nice presentation and not a nice problem for the animal to have.

The pathogenesis of nodular dermatofibrosis and the the development of the tumours is quite poorly understood. But it's thought to be due or linked to a mutation in the folliculin gene. Now folliculin is a tumour suppressor gene.

But the recent hypothesis is that nodular dermatofibrosis might not actually be a paraoplastic disease. So there is, there's a feeling that it might be more just part of an independent dermatological feature of the same genetic disease linked to a mutation in folliculin. So rather than it being something triggered by what's going on with the kidneys, it might just all be the same problem.

And that's because there's been a report really where. But the tumour was removed in a publication, and Adenocarcima was removed, but the tittaneous nodule actually continued to increase in size, which isn't really in keeping with a paraoplastic syndrome. So that there's certainly a sort of a a move away from this just being a sort of classic paraoplastic syndrome.

There's also been a case report describing this modular dermatofibrosis in a golden retriever without a renal tumour and without a follicular m mutation. So it's likely to be more complicated. There's probably other genes involved and then more more work probably needs to be done on this.

But certainly if you look in the older publications and older textbooks, you will see nodular dermatofibrosis, certainly included with the power neoplastic syndrome. So I, I've mentioned it, . In with this group tonight, but it's just, I just wanted to make you aware that it's something that is is is evolving.

Right, on to power neoplastic pemphigus, which is the last power neoplastic condition to talk about. And it's probably one of the worst. So, this is a rare and severe blistering disease and it's quite similar to the rare variant pemphigus vulgaris.

It tends to affect mu mucosal surfaces, the mucocutaneous junctions, and the head skin. And it's been linked to thymic lymphoma, lymphoma, and splenic sarcoma. There's been some some of these cases have been possibly drug triggered, but obviously the majority being paraneoplastic have been linked to these underlying, underlying neoplastic conditions.

Histopathology from taking skin biopsies will, will reveal features of Hemphigus vulgaris, which is quite a deep, blistering disease, of the epidermis and erythema multiforme, so it's a bit of a sort of crossover, syndrome of these two conditions. But definitive diagnosis actually relies on immunological studies to identify the targeted antigens, which is obviously beyond the scope of most of us in, in practise, it's more of a sort of research tool. So as I said, this is a really quite an awful condition to actually see.

Now on the picture on the right here just demonstrates very mild erosions and alterations just at the middle, midline of this dog's tongue. But the middle picture and the picture on the left show much more dramatic lesions. This cat in the middle here has very, very severe ulceration of the tongue.

The gums around this dog's nasal planum, mucus cutaneous junctions, all very ulcerated, and this is the sort of thing that you will see with this condition. This dog on the left, hopefully you can just about make out that we actually have sloughing footpads on this poor dog, so we, you can just about see that where the foot, the footpa epithelium is actually just peeling off from the underlying tissues, so this dog presented in a huge amount of pain, non-weight bearing lane, very, very unhappy, and it really is quite an awful sort of condition, to, to see. This has a very poor prognosis, and that's really because of the severity of the skin changes and the mucosal changes, but also because of the fact that there's obviously an underlying neoplastic trigger.

So even in humans, there's reportedly up to a 90% mortality rate in people that develop paraplastic pemphigus. And that people tend to die from sepsis, multi-organ failure and respiratory failure. So it really is quite an awful thing to, to witness.

It has a poor response to immunosuppressive drugs as well, and, and, and that that's sort of different from other forms of Penhigus, and that's really just because we've obviously got this underlying neoplastic trigger, for this disease. So I hope that not many of you will see that. OK.

And we're now gonna finish up just talking about some of the skin changes we'll see associated with nutritional and metabolic factors. So zinc responsive dermatosis. There are two syndromes that we see, and syndrome one is the one that I think you will see, from time to time.

This tends to occur in northern breed dogs such as huskies, malamutes, and occasionally other breeds. And these dogs will often develop erythema, scaling and crusting, often around mucocutaneous junctions like the eyes, the nose, the the mouth, but also in areas that are subject to wear and trauma such as the elbows, the hocks. And Many of these dogs will actually not be all that bothered by what's going on and if they, if they're relatively mild, it's more what the owner notices and they'll lot of owners will present these dogs to you because of what they've noticed with the, the scaling and the crusting around these areas.

Syndrome 2 is, is, is something that we don't really see so much these days. This is seen in rapidly growing puppies fed a poor diet that is deficient in zinc, which I think is largely historical these days because of most dogs being fed good commercial diets. So here's just some pictures.

So this is a husky dog just demonstrating mild alopecia, mild scaling around the eye. Now this particular dog only had these clinical signs around one eye. Now obviously there was, there were the differentials that would be important to rule out, such as demadiosis, dermatophytosis, bacterial folliculitis.

But in a predisposed breed such as a husky. Particularly if you're seeing scaling, and I appreciate scaling is not particularly advanced on, on this particular case, you know, this would probably need skin biopsies to explore further. These are cases just slightly more advanced.

The picture on the right here just demonstrates again, scaling and alopecia around the muzzle. And again, you'd need to have things like dermatocosis and dermatophytosis high on the list in presentations like this, and then the photo on the left here just demonstrates a more inflammatory picture of dermatitis around this dog's eye. And as you can see, it doesn't necessarily have to be symmetrical, even though this is a metabolic.

Or nutritional problem. So diagnosis of zinc responsive dermatosis relies on compatible clinical signs and histopathology. Normally, pathologists don't have too much of a problem giving you a, a clear idea about what the diagnosis is in this case, because they'll tend to see, the necessary para keratosis, that we need to, that they need to see to, to give you this diagnosis.

But it's also, the diagnosis also obviously, confirmed by a positive response to treatment with zinc supplementation. And signs usually improve over about 4 to 6 weeks with these cases. Another condition that I thought was worth mentioning is lethal achrodermatitis, which I think is very rarely seen, but it, you will see this in all the textbooks.

I thought it's worth mentioning this evening. This is an autosomal recessive conditions seen in English bull terriers. And it has some similarity to zinc responsive dermatosis, but it's more likely to be associated with multiple metabolic pathways, possibly involving zinc, copper and various liver proteins.

Dogs that are homozygous for this mutation develop various clinical signs in the early weeks of life, and they develop a crusting dermatitis on the limbs of the mucocutaneous junctions quite similar to dogs with zinc responsive dermatosis. They can be predisposed to skin infections like due to bacteria and yeast, and then they have some of these other clinical signs which are much more distinctive for these conditions, such as having very splayed digits on their feet and pericia, which means inflammation of the claw folds. They also have a very distinctive arched hard palate, so opening up their mouths and seeing their hard palate being abnormal in young puppies like this would be very suggestive of this condition.

Puppies are described as having abnormalmentation and skeletal retardation. They can develop diarrhoea and bronchop pneumonia, and quite bizarrely, they can often be described as being quite aggressive puppies as well. Diagnosis revolves around compatible clinical signs and histopathology.

Which is quite similar to zinc responsive dermatosis. But there is no effective therapy for this particular condition, and these cases don't respond to zinc supplementation. Unfortunately, the average survival time is only about 7 months for these dogs that are a homozygous affected with the mutation.

So this is really again, not like many of the conditions I've mentioned in this talk, they're not really something you want to be seeing and diagnosing on a regular basis. OK, so just to finish up, we'll talk about superficial necrolytic der dermatosis or dermatitis I should say. This can be a metabolic disease or a paraineoplastic skin marker, so technically you could you could you could describe this in amongst the paraplastic conditions as well.

Metabolic abnormalities are most common, and it's usually associated with a concurrent hepatopathy. And that's where this term hepatocutaneous syndrome comes from. So when superficial necrolytic dermatitis, which is the skin presentation, is caused by this hepatopathy, it's appropriate to describe the problem as hepatocutaneous syndrome.

But SND is also reported with various other triggers, so in those cases it wouldn't be appropriate to call it hepatocutaneous syndrome. And the main other one that has been linked in terms of paraneoplastic, skin disease is linked to glucagonomas and and in humans that's actually the more common trigger for SND. SND has also been linked to phenobarbital administration, diabetes mellitus, intestinal disease, and insulin secreting pancreatic tumours.

The most common form, the hepatopathy. It's thought to be that there's this hepatopathy is in some way leading to a metabolic derangement. Possibly leading to a lack of sustenance for the skin, and that may well be linked to a lack of amino acids.

And that lack of sustenance causes the skin changes of superficial and necrolytic dermatitis. Where it gets a little bit more complicated is how these other triggers of SND that are not due to the hepatopathy directly lead to the same presentation of superficial necrotic dermatitis. So there is still quite a lot to be learned about this condition.

It does tend to be seen in older dogs, and if you look in the publications and the books, there have been some breeds that have been linked and suggested to be overrepresented, which I've listed here, Shetland Sheepdogs, Westies, cocker spaniels, Scotties, and shih-tzus. But this could be seen in any breed of dog. And it has been very rarely reported in cats.

Skin changes start off with crusting, and that leads on to erosions and fissuring. And these clinical signs occur at quite distinctive locations on the body. And it often involves the foot pads and will often involve areas around the mucuscutaneous junctions like around the eyes, around the mouth, but will also involve areas like the pressure points of the elbows and the hocks and the scrotum.

Secondly, microbial infections are very common. And one of the Common findings with this presentation is that these dogs will be systemically unwell because the majority of them have quite severe liver disease associated with this presentation. And it's not, this is, this is something that is a fairly serious end stage type liver disease, so it's, it's normally something that's not particularly subtle.

So these dogs could come in with anorexia, lameness, weight loss, PUPD, and that's largely because of the severe liver dysfunction. So here's some pictures of this condition. This was an old dog, I think in the region of about 12 years old, and hopefully you can see that we have quite, quite sort of dramatic crusting over the bridge of this dog's nose and around the eyes as well, and this dog's obviously under anaesthesia to perform skin biopsies at this stage.

The picture on the right here shows the foot pads of that same dog I just showed you, and at the top of the picture you can just about make out there's quite a lot of hyperkeratosis over the hocks as well. But all of the foot pads on all of the paws are severely hyperkeratotic and or you know, technically we shouldn't really use the term hyperkeratotic because that's a pathological term, but we should really more accurately describe it as scaling. But they're extremely scaly and thickened and fissured.

You can see that there are linear cracks in amongst all that keratin. Picture on the left here again shows marked crusting and scaling and erythema and fissuring in between these areas, so very, very sore, and these dogs are often, you know, very lame coming into the the clinic as well as being systemically unwell. Diagnosis is achieved with skin biopsies and this particular syndrome of superficial and nerolytic dermatitis causes very distinctive histopathological changes, so pathologists are normally not going to have a difficulty telling you what's going on.

If you were to see that back on your histopathology report, then that needs to needs to prompt you to look for that underlying trigger and that often starts with abdominal ultrasound to look for liver, also to look for pancreatic masses, intestinal masses. And on ultrasound, this picture on the left here demonstrates a a normal looking liver and the picture on the right here, it's not the best example, but it does demonstrate that we have some areas of of hypoechoic regions with hypoechoic borders. And The liver takes on a sort of nodular appearance and the classic textbook description would be of a Swiss cheese appearance to the liver.

Obviously that's only going to be found in the cases where we have an underlying hepatopathy. The other cases, linked to nuclearnoma for example, or, or diabetes meats are, are going to have, are not going to have that. As well as skin biopsies and abdominal ultrasound, we need to search for pancreatic tumours, intestinal disease.

It may be appropriate to perform plasma glucagon levels if there is a suspicion about a pancreatic mass, and all of these cases will need to have bloods taken looking for liver enzymes. Many of these dogs are hypoalbuminemic and hyperglycemic, and there's often glucosuria, because they, can be diabetic, associated with this condition as well. Treatment is difficult because remember that most of these cases are going to have a severe hepatopathy underlying this condition.

So it is largely supportive and a cure is, is unlikely to be possible. It's also difficult if there's an underlying glucagonoma, for example, managing that and correctly, correcting that problem is also going to be difficult. But, Certain supplements can be tried in these cases, so it's usually recommended to supplement the diet with high quality protein, sometimes by adding in things like amino acid powders, zinc and fatty acid supplements, adding eggs to the diet, is a good way of giving extra protein, and then sometimes switching these animals onto liver support diets can also be advisable.

Some reports suggest that a better outcome with the administration of intravenous amino acids to these dogs with the hepatopathy, which needs to be given via a jugular catheter, and that's one of the, the drawbacks behind giving that. And surgery would be needed for, conditions like glucagnoma, that's obviously not something that everyone would be comfortable attempting. It is worth saying the prognosis for SND is considered poor, and the reason being that most of these dogs have very severe liver disease, and there's nothing much that can really correct that.

It's just a case of trying to support these dogs as much as possible. But most dogs survive for less than 6 months from the time of diagnosis. So it is again one of these conditions that we don't really want to be seeing on a regular basis.

OK, so in summary, the skin can be affected by numerous internal factors, and I focused throughout this hour on the endocrine, paraoplastic, and nutritional metabolic factors. I'm definitely not suggesting that the conditions that I've mentioned tonight are common, in fact, most of them are pretty rare, but recognition of these changes really helps to ensure an accurate early diagnosis. Thank you very much for listening and I'm happy to take any questions.

Thank you very much, John. Absolutely brilliant webinar. OK, so we'll wait and see if we have any questions pop through.

And just to remind those of you who might have a question, just hover over the top or the bottom of the toolbar and just click the Q&A box to pop your questions through to me. OK, so we do have one from Sally. Is it true that hair code changes can be seen associated with the painful focus directly underneath, for example, increased hair curling over the shoulder or neck with osteoarthritis.

I've heard speakers mention this anecdotally, I think I've witnessed it, but would be interested to hear your views. OK, that's quite interesting. I personally haven't ever encountered that.

I, I'm not sure of the underlying mechanism by which that would occur, but I think it might just be more sort of an anecdotal thing at this stage. I, I certainly have never come across anything in a publication that suggests that might occur. So, I guess I'm gonna slightly sit on the fence there.

I would say I don't think I've seen it, but I'm not completely ruling it out. Thank you very much. I say it was particularly interesting to see the cat with Cushing's disease and the skin changes that you might see with that.

Mm. Yeah, dramatic and not good with the fragility syndrome, that's for sure. No, have you seen many of those cases?

I haven't a few, but certainly, you know, once you've seen those cats, you sort of don't really forget them, that's for sure. Yeah, yeah, I can imagine. OK, don't seem to, we don't seem to have any more questions come through.

So in that case, I'd just like to thank everybody for listening tonight and a massive thank you for you, John, for logging in and giving us your time and such a great webinar this evening. Thanks very much. Thank you very much.

Bye bye. Bye.