Thank you very much, Bruce, and thank you to Webinar vet for inviting me to come back and talk this evening on the topic of new things in dermatology, which is quite an interesting one for me to look into. I've not actually done a topic, this exact topic before. So, when I was, looking into this, I was sort of starting to think what I could come and talk to you about this evening that would be, interesting.

And I guess, we obviously want to talk about the things that have been, new or changed over the last few years. And, I've sort of taken a five year period as, as, as sort of a stop, or as far back as I'm going to talk about, tonight. So just a disclaimer that I have no relevant financial or non-financial relationships within the products or services described, reviewed, evaluated or compared in this presentation.

So the plan for the next hour or so, we're gonna talk about some er some of the new drugs, we'll also talk about some new tests and then also, and, and some new disease descriptions. In terms of the new drugs, well, one that I thought would be particularly useful to go over is the new ear product Necttra, which is just been launched, which some of you may well have already started to use. Cyto Point has been around for a few years now, and I'm not gonna go through all of the studies that have been done on this list, but I thought we could just review, the drug again, and some of the most recent publications, that have been done with this, product just to sort of bring everyone up to date with that.

I also felt it would be interesting just to review the isoxazolines as well. I'm sure you're all using these very regularly in your practises for fleas and ticks, but there have been a few changes to the data sheets over the last few years which I thought we could just review tonight. We'll touch on a palmetto ethanolamide as well, which some of you may or may not have heard of, but that's just something that, maybe, something we could think about in the future for opic dermatitis and an immunotherapy, just a few changes and things for the future as well.

In terms of the new tests, well, there have been a few little changes to allergen serology, which I just wanted to make you aware of, tonight, and then we'll also just touch on PCR testing for dermatophytosis, which, some of you may be doing, some of you may not have done, but we'll just go over some of the pros and cons of that. And then the new new disease description. I could really only come up with and find one that I thought would be interesting to talk about, that's really been mainly described over the last years or so, and that's mucocutaneous lupus erythematosis.

So we'll go through all these in order now. So new drugs. So Netra, so what is this?

Well, it's the new topical ear product from Bayer, and this, in keeping with the other licenced ear medications for dogs is a triple pharmacy product containing an antibiotic, a steroid, and an antifungal. And the USP of this product is that it's the only single application topical ear product available, so it's the vet administers this product into the dog's ear, and then that's all that needs to be done. So no owner administration at all, which obviously sounds very appealing.

It comes as a clear, colourless to yellow, slightly viscous liquid in a single use sealed tube, as can be seen in this picture, and these tubes contain 1 mL of the solution. Just a little bit more detail about what's in it. Well, memethazone fluorate is the corticosteroid, and it's a high potency steroid.

So some of you may well be using the already licenced product Poserex, which also contains that steroid as well. But it is a potent steroid and one of the other advantages is that it's, it really has sort of quite limited systemic absorption as well. Tabinophen is in there because obviously to treat malasthesia fungus in the ear that we deal with so often.

Tabinophen is an allo amine and antifungal which inhibits ergosterol synthesis in a slightly different way to the azoles, but ergosterol is a central component of the fungal cell membrane, so it's in there to principally get malathhesia. Chlorphenacol is a bacteriostatic antibiotic which inhibits protein synthesis, and that is mainly active against gramme positives. Some gramme negative bacteria, but it's important to note that the in vitro activity of that antibiotic is low against bacteria like pseudomonas.

This has been launched licenced dogs. It's not it's not the cats, and the data sheet states that it's for the treatment of acute otitis externna or acute exacerbations of otitis externna caused by mixed infections of bacteria sensitive to the antibiotic and fungi susceptible to tobinophine. So it's principally going after those first type presentations that we see so commonly in general practise.

And obviously stashud intermedius is a very common, bacterial cause of otitis externa and malacasia is very, very common, as the fungal component. So that's what it's been mainly designed for as, as, as those first presentation otitis cases. And at present it's not licenced for ear mites.

I know some of the other tropical ear products in the UK do have an indication for ear mites, but this does not. So how do we apply it? Well, The data sheet tells us to shape the tube well, and we do need to clean and dry the ear canal first of all.

And in the studies that were done as part of the launch of this product, that cleaning was done with saline. So that's just worth mentioning because obviously, in, in normal, general practise, day to day practise, that's probably unlikely to be the thing that you would necessarily reach for to clean a dog's ear canal out. So if you're going to clean the ears out with one of the other, many ear cleaners that are around, we just don't really know, and the manufacturers they don't really know how that would impact on the efficacy of this product.

So that's just a a a word of caution there. Obviously there's, it may have no impact but we just don't really know. The entire one mil of the tube is then squeezed into the dog's ear canal.

And the ear is then gently massaged for about 30 seconds, and ideally wanting to restrain the dog's head for about 2 minutes after that to try and prevent head shaking, and we all know that's easier said than done. Apparently it's also quite normal for the ear to look wet our application, and I will just add that I haven't actually used this product yet myself, partly because of the restrictions over the last few months we've all been going through, the dermatology service, at the hospital I work at, has been somewhat restricted in terms of seeing cases. The maximum effect may not be seen for 28 days, so obviously that's quite a long time, it's worth persevering with seeing clinical improvement over that duration.

What about contraindications that are listed on the data sheets? Well, as with all of the other, polypharmacy ear pre preparations in the UK, it's advises us not to use if the tympanic membrane is perforating. Also to not use in pregnant or breeding animals and to not use in cases of generalised demidiosis, probably because of the corticosteroid component.

And the data sheet also specifically advises against ear cleaning or further air cleaning until after that 28 days, because obviously that's going to have an impact on the the product that's in the ear. So that's, that's just worth mentioning because as part of treatment for some ear cases we do need to factor in regular ear cleaning to keep the ear free of discharge and sumen. So there may be some times when this product is not the ideal one.

And the day she also says that the the safety of the product has not been established for the dogs less than 3 months of age or for those weighing less than 4 kilogrammes. However, there are no risks to dogs less than 44 kilogrammes were identified in the safety studies. It also advises us to be cautious in dogs with underlying endocrine disorders like diabetes mellitus or hypo or hyperthyroidism.

Again, presumably because of the corticosteroid component. And we also need to be careful about contact with the patient's eyes and also the administrator's eyes. So that this product has been, is known to cause irritation to the eyes, so there is a suggestion that the administrator should be wearing protective goggles.

In terms of side effects or adverse effects, only things that have been reported very rarely, and the definition of very rarely is less than 1 per 10,000 treatments. So you get the idea that this is not a common thing, but the data sheets states vocalisation, head shaking, and application site pay shortly after application have been noted. And then other adverse effects include ataxia, internal ear disorder.

And nystagmus, emesis, applications like erythema, hyperactivity, anorexia, and applications like inflammation also very rarely reported. So these are not, you know, you wouldn't be expecting to see these, but it's just worth being aware of what's mentioned in the data sheet for any new product. So I'm sure some of you are already starting to use this product, it really does look to be a very useful addition to the market, because of this USP that it's a single application product owners I'm sure are going to like this .

The equivalent product to nectar, which is actually goes by a different name in the, in the USA of Claro, has been around for a little while and it's done extremely well. So I'm sure in general practise, many owners are gonna, you know, like using this product, but it's important to remember that this is aimed at those first presentation type cases. So, if you've got a pus filled studentomonas here in front of you, it's probably not going to be the products for you.

OK, moving on to Cyto point now. Now I'm sure many of you are quite familiar with this, it's been around for a few years, and you're probably using this quite commonly in practise, but it's worth just reviewing what it is. It's a canonised monoclonal antibody which has been expressed through recombinant techniques in Chinese hamster ovary cells.

So it's, it's the very first licenced monoclonal antibody therapy in veterinary medicine. And it comes as an injectable solution for the treatment of atopic dermatitis, and we give that injection subcutaneously at monthly intervals. It has a very unique mode of action because the monoclonal antibody specifically targets interleukin 31, which we know to be involved in pruritus in dogs.

And by binding to that interleukin, then that interleukin then does is not able to trigger the er downstream signalling cascade, and, and cause its effects. So looking at the data sheet of this product, well, are there any contraindications or warnings? Well, this also says to be not used in drugs less than 3 kg because it's very difficult to be accurate in terms of dosing of such small patients.

There's also a mention in the beige sheet of anti-drug antibodies. Now because this drug is a is a monoclonal antibody, it's a protein, there is the possibility the body's immune system can then over time react to the drug and form antibodies to the to the monoclone antibodies. In some cases that there is a concern that could actually then result in a loss of efficacy of the drug, or potentially it could end up, you know, causing no effect.

But I, but I guess it is a concern with this particular drug because of what it is being a monoclone antibody, is that it could result in loss of ficacy over time. And this is very anecdotal, but I feel that over the years I have been using this, I do feel that this does occur in small numbers of dogs that we use this on. The data sheet also says that if there's been a minimal response after one dose of this drug, then we might then get a better response if giving it a second time, so it's worth persevering even if the first, the response to the first injection has been, not as good as you would have hoped, giving that second dose and seeing.

In my experience, I think usually sighted Point works very well, for, for, you know, a, a good subset of dogs, after the first injection. So I'm not sure, in my own experience, I'm not necessarily sure I've seen this, but, but certainly I'm, you know, I'm sure some of you will have done. The safety has also not been established during pregnancy and lactation, but one of the really nice things about side of Point is that there aren't drug interactions observed to other medicinal products such as endoenective paraiticides, antimicrobials, anti-inflammatories and vaccines.

So unlike some of the other drugs that we Have available for the treatment of atopic dermatitis in dogs, cycling point really doesn't interact with a lot of the other drugs that we may be using in those patients and therefore it's, it's a, it's, it's a commonly used drug if there were other comorbidity. In terms of adverse effects, well, we listed our hypersensitivity reactions rarely, and that the definition of rare reactions is between 1 and 10 for 10,000 treatments. So, urticaria, facial edoema right up to anaphylaxis has been reported.

In my experience, I, haven't seen this, but I have heard of, rare, instances of this happening, after or, or, or, or thought to be linked to cyto point injections. Vomiting and diarrhoea, rarely as well, and then also seizures, ataxias, ataxia and convulsions have been rarely, linked to this drug, so, it is just worth knowing, that these, these have been linked to this drug and just being aware of them. So, I just thought I'd just present a just a couple of the recent studies that have been done with, with Cyto Point, and.

One was published in veterinary dermatology in 2017. This was a blinded, randomised non-inferiority trial evaluating LocuvetMb cyto point against cytosporin, obviously a licenced drug for atopic dermatitis, and in this study they took 274 client owned dogs with atopic dermatitis across Europe. In this study, they were randomised to receive either Loki vetMab or the or or cyclosporin, and they received that for 3 months.

81 dogs that completed the initial comparative phase of the two drugs then undertook a continuation phase whereby they received Loki vetMab, the the cyto point for a further 6 months. And then throughout this trial, the owners assessed a pruritus visual analogue scale. Which is a scale of, of, of how bad the pruritus is, and skin lesions were recorded with something called CDO3, which is a skin lesion scoring system.

Both this, both the Kinesio 3 and the PVAS scales are commonly used in studies for atopic dermatitis, so you will see this if you look in the literature. In this study, Loki vetmab was found to be non-inferior to cyosporin for pruritus reduction on day 28, which was a sort of benchmark thing they were looking for in this study. Non-inferiority for lesion reduction, the Cadizio 3 actually was not achieved though, statistically in this study, although the mean Cadizi scores actually did not differ between groups at any point throughout this, this, this, this trial.

And in in the continuation phase whereby those dogs then received the monoclonal antibody for the months afterwards, 76% of those were assessed as normal for their level of pruritis at the study ends. That's a, you know, that's a good percentage of dogs reported to be normal. In terms of adverse effects in this particular study, none were actually, recorded to Lokitab through either phase of the trial.

But 3 of 142 animals did develop anti-drug antibodies which were being measured throughout this trial, and there was a feeling that in one dog that may have contributed to a reduced efficacy. So that just ties back into what the data sheet tells us about these anti-drug antibodies and that it's a theoretical thing that could happen and we just need to be aware that it's possible. Another study that was published again in veterinary dermatologist a year later, this was a retrospective analysis of er vetmb cyto point.

I mean 135 dogs for allergic pruritus. This wasn't just atopic dogs. This was dogs with undetermined allergic dermatitis and also adverse food reaction.

And in this study, they found that 87% of dogs showed improvements in their in their pruritus. And 77% showed greater than 50% reduction in the level of their pruritus, which is a common measure used in studies on atopic dermatitis. Interestingly, in this study, they actually found a higher odds of improvement for dogs with either severe or very severe pruritus.

And also in large or giant breed dogs, which is sort of an interesting thing why that might be. But they found no association with the age of onset of the skin disease, the dose given or the disease duration. They also found that dogs who'd showed a prior poor response to Oplacitinib or Apaquel were also less likely to respond, which in some ways sort of makes sense because of their sort of obviously have different modes of action, but they have some similarities.

In terms of adverse effects, they found in very small numbers of dogs, lethargy, vomiting, hyper excitability, pain at the injection site and urinary incontinence, it was only in a low numbers of dogs. And then in a more recent study that was only published last year, again in veterinary dermatology, this study, looked at proactive maintenance therapy, using lowkey vetM for atopic dermatitis to see how effective the drug is at preventing flare-ups of disease. And in this study they took 21 dogs with spontaneous atopic dermatititis, who had these dogs had been on various treatments before entering into this study, and these dogs were transferred across onto Loki bet.

All of the drugs were then withdrawn over 4 weeks, and those dogs were then followed for at least 1 year with the monthly cytopoint injections, and the time to flare was then recorded. The median time to flare in this study was 63 days. A quarter of those dogs did not flare at all for at least a year, which obviously sounds good, but half of all dogs did flare within 2 months.

And it's just interesting to note that the time to flare was only about half that of the time to flare shown in a study whereby the dogs were receiving twice weekly topical m to corticoid therapy. So in some ways the the the time to flare was not particularly encouraging. In this particular study for, you know, decent subset of the dogs, and the investigators concluded that the drug certainly can delay flares in some dogs with spontaneous disease, but certainly not all, and further investigations are probably needed to sort of try and work out which dogs are more likely to respond to that particular therapy.

So in terms of a summary of scito points, it, it, it was obviously an extremely welcome addition to the treatment options for atopic dermatitis for, I'm sure you all have your own opinions on how on how effective cytopoint is, but, for some dogs, it does seem to work extremely well. It's well tolerated with very minimal, adverse effects, and another real advantage is that it's very quick to work, so often the beneficial effects will be seen within 8 hours. It is expensive and there's no doubt about that, but then, you know, there's a lot of science has gone into the creation of this therapy, so it's not a surprising, it's also new.

And I guess like with any drug, it's not effective in all cases and particularly with a drug like cytokine, which is such a targeted therapy to one particular interleukin, it's not really a surprise because atopic dermatitis has such a, such a. A, a sort of complicated pathogenesis, and it's clearly more than just one cytokine involved, so it's really not a surprise, but that's certainly a very, very welcome addition, and, we, we use it quite commonly in our hospital. OK, moving on to the Izoxyzolines.

Well, these are a group of aca aides and insecticides, and I'm sure you are all using these day in and day out, in sort of every practise around the country. They act antagonistically on the ligandated chloride channels, the gabain glutamate receptors in the CNS of these parasites and insects. So they, they're, they're sort of neurotoxic.

And they've been licenced in dogs and cats for a few years now. And they were initially licenced for fleas and ticks, but it was quickly realised that they were effective against more than just fleas and ticks and against various mites as well. So over the last few years we have seen some changes to their licences to include some of these mite infections as well, and that's what I sort of wanted just to draw your attention to tonight.

So here's a chart. This is the, these are the ones for, for dogs. I'm as I said, I'm sure you're using these commonly and most practises will stock at least one of these, but it's worth just showing that all of them really are licenced for fleas and ticks, but you can see that the top 4, well 3 drugs which are Saulena, fluorena, and oxyena, also have licences for sarcotes, and also Demodex.

And just a particular note that Saullena also has a licence for Otodectes . And dogs as well, you can see at the bottom, Lottelena, which is the newest one to the market at the moment, does not have a licence in the UK for sarcopy and Demodex. I, I don't know if that may change in the future, but it's at the moment at the time when I was preparing this talk, it does not.

So the isoxazolines are now one of the preferred treatment options for canine demidiosis. I mean, we, we do still get quite a lot of advice calls about cases of Demedex and how best to treat them, and that's why I thought it would be worth just discussing this tonight because they are really one of the best treatment options for cases of Demedex now in dogs. And there's a very, very recent publication produced on behalf of the World Association of Veterinary Dermatology.

Who, this organisation has been producing some clinical consensus guidelines for a few years now, and really only a month or two ago they published, these clinical consensus guidelines on the topic of demidios and dogs and cats, led by Ralph Mueller, who, who works in Germany. So this is, these, these publications are open access, so if anyone's interested, these are really excellent review articles on some important topics in veterin dermatology. So if you go on to the WABD website, I think you can access them directly through there.

So in this publication, they evaluated the treatments available for their mediosis and concluded that there are several effective therapies. And they included weekly amatetraz rinses. Now we've obviously had that available for many, many years in the UK, and that was always the go to treatment for canine demidiosis, but obviously it had some drawbacks.

It involved clipping of the coat in long-haired animals. It was not a nice treatment to use for both dogs and owners. And it was really quite labour intensive having to do these weekly rinses.

Other effective treatments that were advised by these clinical consensus guidelines included oral ivermectin daily, moxidectin orally daily, milbamycin oxime again orally daily, and then also weeklytoramectin injections subcutaneously, but none of those options are licenced, obviously Amatraz has been licenced for many, many years, but these other options were always having to be used off licence. We also obviously had a further licenced product which was the topical moxidectin amid a crop which spot on that we've been had available for a while and we've been using, but because over the years there's been a realisation that that product is, is not as effective as we would all like it to be, the latest guidelines from this publication state that this should probably be considered more for mild to moderate cases of canine demiticosis. But the guidelines did conclude that the isoxazolines are an excellent treatment choice.

There is enough published data to support them making this recommendation, an excellent treatment choice for demidiosis. As I mentioned, Lotallana, the newest one, is not currently licenced, so my advice would be to use one of the 3 licenced, tablets, but they do seem to be very effective for demidiosis. They're obviously easy to administer, these are just kind of tablets, which are often being used as part of routine, parasite control.

And they do have very minimal side effects, so mild and transient GI side effects, lethargy, although there have been some, reports, case reports in the literature in rare cases of things like neurological, neurotoxicity like ataxia and convulsion, but they are very rare. So summary of the Izoxazolines, these are an excellent choice for canine dermaticosis as a first line option for cases. And I think many dermatologists would have these as their preferred option for treatment now.

They are safe and well tolerated, they're licenced. And they can also be continued in the long term because obviously over the years we've been taught that we should treat demiosis cases until two negative, skin scrapings that's the sort of general rule of thumb, but. Often in in cases of demidiosis, we can just continue giving these tablets ongoing as the monthly or every 3 months in the case of fluoroina routine, parasite treatment.

So you don't have to stop treatment as such. An interesting point just to mention though, is, could that actually be a problem though if we're using a drug that kills off Demodex populations in the skin? Could that end up actually being a problem for some dogs, because we know, and we're taught that Demodex mites are normal inhabitants in low numbers in the skin of dogs and.

If they get killed off, maybe they are having some beneficial effect on the microflora of the skin and their absence might allow other microbes, for example, to, to change and may end up actually provoking a problem. We don't know the answer to that question as to whether that may be a problem, but it's just something that's interesting to speculate on. What I do think though is that I think these tablets are making demidicosis rare.

Certainly, I, it's been a very long time since I've seen a case of canine demidicosis referred to the clinic at the hospital I work at. So I think it's, I, I, you know, my, my feeling is that it's going to make it a much rarer disease. OK, so moving on to a slightly different topic now, Palma or ethanolamide, which often gets short, shortened to PEA for fairly obvious reasons.

Atopic dermatitis affects up to 15% of the canine population, so this is something we see day in and day out in practise. And the latest treatment guidelines for atopic dermatitis. Advise trying to use a multi-modal approach whereby we use different therapies to not just, you know, pump the dog full of something like a steroid but but try and address all the components of that are contributing to the pathogenesis of the disease.

So we need to avoid flare factors. We need to consider the skin and coat hygiene and try and improve it where possible. We need to try and control secondary microbial infections which we know to be.

And these dogs to be quite susceptible to. We often like to add in immunotherapy because that's the only treatment that can actually alter the course of the disease. And then we also need to obviously use symptomatic medications such as Loyvetabbs, such as corticosteroids, as well in some cases, as an anti-inflammatory.

But the best control of atopic patients is achieved by trying to approach these different aspects of the disease. So what is PEA? Well, it's a naturally occurring bioactive lipid compound and an endocannabinoid-like molecule.

And the endocannabinoids and related mediators are produced on demand in the body in response to stress and tissue damage, where they help to regulate cutaneous information and are involved in immunity. They may also have actions on mast cells, but there's a feeling that they help to reduce itch and pain. And it's been shown that levels of Palma or ethanolamide are actually about 30 times higher in the skin of dogs with atopic dermatitis.

Now ultra micronized PEA. Or PEA to stand for the ultra micronized, is a pharmaceutical grade formulation of PEA and the PE, the ultra micronized part of it increases the bioavailability. And there have been a few studies looking at PAM in animals with allergic skin disease, and I just thought I'd just mention those this evening.

So Chiara Noli, who's a very eminent dermatologist in Italy, published in 2015, an open label trial with 160 client to dogs that had moderate atopic dermatitis. So these dogs weren't really severe, tearing themselves to bits. They had moderate clinical size.

And in this study, they, which was over 8 weeks, they gave these dogs PEA and no other other symptomatic drugs were allowed apart from immunotherapy if it had been going in the background. And this open label trial showed a significant reduction in clinical lesions, in pruritus, and the general increase in quality of life. But you have to remember in these sort of trials that this was not a double blind placebo controlled trial, so therefore it is a bit more open to bias.

And only 4 dogs showed mild side effects which were GI related in this small in in this trial of 160 dogs. So it seems to be well tolerated. Kiara's group then also did a study just last year, again looking at PEA but this time in cats with non-flea hypersensitivity dermatitis, that would be allergic dermatitis that could be due to environmental factors or potentially food, food, triggers.

And in this, in this study, 25 cats were randomly divided into treatments and placebo groups this time, so it was a placebo, there there was a control group in this particular study. And initially clinical signs were controlled over 28 days with tapering methyl prednisolone, a drug that we would expect to be effective for this, for these cats. And then after that time, the responders received either the placebo or PEA on for another 8 weeks.

And in this study. The time to relapse was, was, was assessed and it they showed that there was a significantly longer time to relapse in the treatment group compared to the placebo. They also showed that a global assessment score of how the animal's allergic dermatitis was was also lower for the treatment group at the end of the study.

So There's not much information on this, but some study data sort of to suggest that it might have a beneficial effect as part of management of atopic or allergic skin disease. So it might be something promising, for the future, as in terms of managing allergic patients, but we do need more studies to confirm those initial findings in just these small and and a couple of studies. Now PEAO was initially marketed as Redinil Ultra by DeRA, but it's actually no longer available at the moment because I think as far as I'm aware, there was, it was sort of initially launched as a sort of supplement, and I, I think there was some con some concern, from the regulatory bodies that it was more of a medication.

So at the moment it's been withdrawn, but it's just something that I just felt. Because it's been mentioned in some studies, I thought I'd mention it tonight that it may be something that may become available again in the future, and it may be something that may help overall management of our allergic patients. Now immunotherapy, this is certainly not a new er treatment, this has been around for decades.

As I'm sure many of you will know, it's the only treatment of atopic dermatitis that can change the pathogenic mechanisms of the disease. We don't really know for sure how it works, but it's thought that it might well activate regulatory T cells and regulate immunosuppressive cytokines, which then subsequently help to improve clinical science. And most data is available for dogs, not much available in cats, but even in dogs, there's, there's not a huge amount in the literature.

And I thought I'd just mention a few areas that have been looked at a bit more recently in terms of immunotherapy, one of which is adjuvanted immunotherapy. This has been investigated in a few pilot studies, the principle being that adjuvants stimulate the immune response to produce an improved efficacy and increased safety. So, examples of adjuvants include things like bacterial oligo deoxynucleotides and Pulaan and manan.

And there have been some studies whereby the immunotherapy's been . Adjuvanted with these substances to try and improve the efficacy. And in the small pilot studies that have been done, the results have been fairly promising, but they've only included quite small numbers of dogs and we really do need larger randomised studies.

So it's something that may become more available over the coming years. Sublingual immunotherapy or all immunotherapy, have been available for some years now and they used quite a lot in human medicine. But I just thought it was worth mentioning because, sublingual immunotherapy is available for dogs.

It might not, I don't think it gets used very often, but there are some instances when. It may be more appropriate or easy to sort of easier for owners to to think about using. It could be in animals that are particularly needle shy or maybe the owner's needle shy.

Sublingual immunotherapy is where the extract is actually applied between the lips and gums of dogs, once to twice a day. So it's not the monthly under the skin injections of traditional immunotherapy, it involves very regular, under the skin applications of the liquid, which is not for everyone because for many owners that they'd find that more labour intensive to remember to do it that often. But for some animals, it does seem to be an easier option than than the monthly injections.

And generally in the small numbers of studies that have been looking at this, the efficacy seems to be similar to that of subcutaneous immunotherapy. But there was a suggestion. Doug Doug De Boer is an American dermatologist, that, in 2012 published this report showing that some dogs seem to improve with sublingual immunotherapy even if they'd failed the traditional subcutaneous immunotherapy, so.

In those dogs that er immunotherapy has not been effective, we sometimes do suggest that they could try another type of immunotherapy, the sublingual immunotherapy. But in my experience, and in the clients that I see at at hospital, many owners are not willing to do immunotherapy a second time, they've normally, normally they'll do it once and then they've had enough of it and want to move on to something else. But it's just worth mentioning that it's, it may be easier for some dogs and it may provide some extra benefit even in those cases that failed the traditional one.

And then recently we've had a few publications of intra lymphatic immunotherapy. And this is where a smaller amount of allergen, normally 0.1 mL, so it's quite a bit less, is injected directly into the lymph node and it's normally the submandibular popliteal lymph nodes at monthly intervals.

It's been reported to be safe and quite well tolerated, which is surprising because it doesn't sound like a particularly nice thing to do. But based on the information to date, . One of the advantages of doing this was in the hope that by putting it directly in the lymph nodes, we might get some longer lasting benefits, you wouldn't need to keep giving regular injections.

But based on the information so far, long term benefit only seems to be seen in quite a small number of dogs, and most patients do need to have continuous intra lymphatic injections, which then I think not many owners would particularly see the advantages of that. So we need more studies, but it's just something that I thought I'd mention that may become something for the future. So in terms of summary for immunotherapy, we've had the traditional subcutaneous immunotherapy available for decades.

It's certainly a recommended and established treatment for atopic dermatitis. It does seem to be very safe, very few recognised side effects, and you're probably all familiar with this 60% response rate which is generally, mentioned in, in most textbooks and in most reports, I think that's, it's always quite hard to know whether that's really the case because we could always have an element of, placebo response with, with owners wanting the therapy to work, we just don't have many or we actually only have one, double blinded placebo controlled trial of immunotherapy, in the literature. It's just so hard to do these studies because they need such a long period of investigation where everything else is controlled.

Sublingual immunotherapy could be an option for some dogs, as we mentioned, and an intra lymphatic immunotherapy may well be an option for the future. OK, now on to some new tests. Now allergen serology is obviously not a new test, that's been around for ages and I'm sure most of you are doing this, you know, certainly maybe not day in, day out, but certainly, you know, every week I'd say.

In general practise, a common thing to need to think about doing in, in allergic dogs, with, with you suspect have atopic dermatitis. But as with intradermal testing, this testing is not used for the diagnosis of atopic dermatitis, it's used to detect sensitization. Which may then be a useful guide to what might be involved in what's contributing to that particular patient's allergic dermatitis.

So we, we, we use it for either to try and avoid allergens, which is often very difficult, and maybe even impossible. More often it's done to try and identify allergens for inclusion in allergens specific immunotherapy. Now for some time, some clinicians have felt that we have tended to get quite a lot of false positive results on allergen and serology tests.

And there's been a feeling that they might be more common than we see with intradermal testing. So we sometimes have in the past have seen results where you get loads of positive results to the pollens of trees, for example, or weeds, or all the dust mites allergic, and in vitro cross reactivity has been a concern. Now one possible explanation for this is cross reactive carbohydrate determinant.

Or CCDs and what are they? Well, CCDs are defined carbohydrate portions of plants and insect glycoproteins. And anti CCD IGE or antibodies to these carbohydrate determinants.

Have been detected in humans and they're a a known thing, a recognised thing, and they're thought to be clinically relevant, so tests that might detect those in humans have known that really they're not significant and not likely contributing to that particular patient's allergic disease. So there's been some concerns or increasing concerns over recent years that some serological tests that we may have been doing for in animals might have actually been detecting these antibodies to these CCDs, therefore giving us positive results to things that actually weren't really clinically relevant for that particular patient. And I'll just draw your attention to one recent study which was published just last year.

And in this study, they showed that intradermal testing. Correlated best with serum test results when there was no evidence of anti CCD IGE which which would then support the fact that this, these antibodies to CCDs might be significant. And they also then showed that the serum that contained anti CCD antibodies had multiple positive results of grasses and weed allergens.

And those are the ones that showed no agreement with the intradermal test results. Now in this particular study, what they did was they showed that by then using a solution that can, that blocked those antibodies to the CCDs, the agreement of the serological test with the intradermal testing could be improved, which then obviously supports the theory that these anti CCD IGD antibodies were being removed and not being, they were not clinically relevant and the test was being improved by getting rid of them. So why mention this, what's the outcome of this?

Well, it's just important to note because many laboratories that we use in the UK testing, doing, performing allergens tests have now started to test for these anti CCD antibodies on samples that we submit to them. So if you form allergens toology, and you sometimes see at the bottom. Of a report back from them and there's a little sort of paragraph about anti CCD antibodies and the fact that these labs are starting to test for them.

So what they'll do is they'll detect whether they're there and if they are there, they'll use one of these blocking solutions to to remove them and hopefully give us some improved results which are more more a better accurate idea of what that animal is truly sensitised to. And that might then have a better impact on what we might then choose to put in immunotherapy. So that's just what I wanted to mention because you will see that at the bottom of some of these reports.

PCR testing for dermatoytes, this is obviously changing topic quite a bit now. This is a relatively new test to aid in the diagnosis of dermatophytosis, but. There is no one single gold standard diagnostic test for dermatophytosis.

We always have to use a combination of diagnostic tests to try and aid in the diagnosis, because even something like a fungal culture has pros and cons. How do we perform a PCR test? Well, it's a little bit similar to a culture in that we need to try and gather up hairs or skin scrapings and squains that may be infected and we collect those up and submit them to the laboratory.

And the lab normally does a PCR to identify to genus level initially, and that would normally tell us whether we're dealing with a microsporum species or trichophyin species, and then that will be then followed by a species PCR if the result is positive. And PCR claims to be very sensitive and also specific. The main advantages of doing a PCR test are that we should get the result back in a matter of a few days, 2 to 4 days rather than several weeks of a culture.

So it's obviously much quicker at giving us an answer, which is obviously advantageous to us and also to own. But is it a useful test? Well, It is a useful test, but we do need to be quite clear in terms of what a positive result actually means and what it's actually telling us.

So if we have a positive PCR test, then what, what it's telling us is that fungal, dermatophyte DNA has been found. But we know that that could be because there's an active infection, so obviously a positive result could mean an active infection. But we also know that animals are capable of carrying fun fungal species like dermatofites on their coats subclinically just aroite carriage.

So we need to know that that a positive result on a PCR test, like in a with a culture, doesn't absolutely tell us there's an infection, it just tells us that we've demonstrated fungal DNA. Because this test is also very sensitive and it detects the DNA, it is also possible that a positive result could be seen following treatment, just detecting non-viable fungal organisms that have been killed with the effective treatment, so. One of the concerns is that it could, we could get a positive result if you're just using a PCR at the end of treatment, even though the animal is treated and cured, you might get a positive result and that might, in some cases prompt you to continue treatment for longer than is necessary.

So it's a highly sensitive and specific test for the presence of the dermatophyte DNA. It does give us a quick result. It's very useful in that regard, but it's just very important we remember what a positive result means.

And for that reason, because we can detect this non-viable fungal DNA and we have this romite carriage concern, it is best for confirming the initial infection. It's not as good, it's not as useful for detecting the end point of treatment. So for that, we.

Probably should be relying more on clinical signs and fungal culture which will detect viable fungus that can grow as a means to detect when treatment can stop. OK, so we, just into the last 10 minutes now, and we're just gonna finish up with a disease, a new disease descriptions, and as I mentioned already, there's really only one that we need to talk about that I thought I thought it'd be interesting to cover for, for this evening, and that's mucocutaneous lupus. There are various forms of lupus erythematosis in dogs.

I'm sure you'll all be familiar with systemic lupus erythematosis. This is something we all get taught about in our university days. Well, actually it's a very rare disease and it's also notoriously difficult to diagnose because .

As the name suggests, it involves systemic involvement, and it's not just skin signs. We can have a whole host of different, clinical signs internally as well. And it's this, you know, we just don't have time to go into details of that tonight, but that one, is the, is not it's one of the most difficult diseases to, to diagnose because the clinical signs so varied.

We also have discoid luposerahematosis, that's probably the most common one, that is one that you probably will see, and that can be in classic forms which tends to be sort of facially predominant, often on the nasal planum as is shown in the two photos on the left and right of the screen here. There's also rare report of a generalised variant of disco lupus erythematosis, but it's the classic one that I think you will see from time to time. We also have exfoliative cutaneous lupus erythematosis, which is a very rare presentation, one I've actually not seen before.

It's been reported in German shorthead pointers and vesicular cutaneous lupus erythematosis which the dog in the middle picture shows this. This is where we tend to get, again, it's, it's skin only, but it's where we get these erosions and sores and in the early stages vesicles, as the name suggests, often with a ventral distribution in coll type breeds involving underneath the groyne areas like that, but can also involve around the mouth. I think you will see that potentially from time to time.

But over the years, there have also been descriptions of some dogs presenting with a slightly different pattern, with a more of a chronic juxta mucosal erosive presentation, but also with histopathology typical of cutaneous lupus erythematosis. And in the isolated case reports that were over the years, they, the investigators termed, did use the term muscutaneous lupus, but they also used discoid lupus erythematosis and perianal and periolal lupus erythematosis to try and describe this presentation. But in 2015, which I know is a few years ago now, Thierry Olivery, who's a very eminent, if not one of the most eminent dermatologists in the world actually, who works in America, and published a case series of 21 dogs trying to bring this condition together and define it in more detail.

And they, and Terry and others in this publication proposed the term mucocutaneous lupus erythematosis or MCLE. To describe this novel variant, and I'm just gonna present that paper to you, tonight just to show you some pictures of what this looks like. So here's the paper.

This was published in 2015 in veterinary dermatology. It's a really, really nice, review of this condition. So if any of you have access to this, journal, it's a, it's a good one to go and have a look at.

In this paper, various breeds, cropped up, but actually 11 of 21 of those dogs were German shepherd dogs or their crosses, so there did seem to be this predisposition for this, these breeds. They also found that females were possibly predisposed to this condition as well. The age of onset was variable, so it ranged from between 3 and 13 years, but mid-adulthood was most common, which actually is in keeping with many autoimmune diseases.

The clinical signs consisted of erosive lesions and often around the anus and genitals, but also sometimes around the eyes, the mouth, and the nose, but all mucocutaneous distribution areas as the name suggests, and it being an immune mediated problem, a degree of symmetry was seen as would be expected for this type of process. Most dogs have more than one side affected, and that's sort of what you'd expect for something that is involving the immune system, but not all of them. So some of them have more localised disease to adjust around the anus or the genitals, for example.

Some of these dogs, because of where the lesions were showed signs of pain when defecating and urinating. And an interesting sign was also areas of hyperpigmentation of the skin in in the skin around where these erosive lesions were. So that's one of the things that this that Olivery and colleagues in this study mentioned to look out for as one of the sort of hallmarks of this condition.

And because this is a skin only variant of lupus, there were no systemic signs other than those mild ones associated with the discomfort. So here are just some of the pictures. These are taken directly out of Terry's publication, which you can see at the top of the screen.

So you can see that we in this condition you can really have some have some quite severe and nasty lesions. The pictures on the left here just show erosive lesions around the vulva, of dogs and then the ones on the right, obviously around the lips, and you know, these dogs you can imagine would be, would be quite uncomf. In terms of diagnosis, you do need histopathology, so biopsies to diagnose this condition, and all of them, were in this, in this case there were consistent with cutaneous lupus erythematosis.

Lupus, is an interface dermatitis, so we have a lymphocyte rich interface dermatitis with evidence of basal cell apoptosis, which is what a pathologists need to look for to, to be able to diagnose it. And most cases were negative anti-nuclear antibodies. That's something we tend to see more of in the stem systemic variants.

In terms of treatments, well, there were various that were mentioned in the 21 cases, but they included oral corticosteroids, niacinamide, which is the B vitamin with cycling antibiotics. I'm sure many of you would be familiar with the use of tetracycline and niacinamide as a combination for mild immune mediated conditions. Topical tacrolimus, tacrolimus is a topical calciumurin inhibitor, in a similar, with a similar mode of action to cyclosporin, topical corticosteroids and oral cyclosporin as well.

And the doses were generally standard, for immune mediated conditions. In these 21 dogs, none showed a spontaneous recovery, but complete remission was obtained in all but once. That gives you the idea that with treatment, the prognosis should be pretty good.

The median times remission was 30 days when corticosteroids were used orally, but it was actually 60 days when no steroid was used, so the, they, they did report that they felt steroids were were were better for this condition and should be considered for these cases. And 82% needed treatment in some form in the long term, so this is something that isn't probably gonna go away, and not many dogs are going to remain in remission of drugs in the long term. So in summary, mucocutaneous lupus erythematosis is a novel variant of cutaneous lupus.

And it's important to consider in dogs with mucocutaneous erosions, particularly if we're dealing with female German shepherd dogs or their crosses. And I think it's quite an important condition to be aware of, and it's one of the reasons why I wanted to mention it tonight because we, I'm sure you all see these female dogs that present with perivolval ulceration and, and nasty pseudomonas type infections, and there's a feeling that it's due to. Volval fold infections and things like that, where an anatomy might be contributing, but I think this is an important differential to have on the list in those cases because obviously if you have this condition causing severe erosions and ulcerations, that those lesions could quite easily then become secondarily infected over time with bacteria like pseudomonas.

So it's just worth remembering that there could be an underlying cause for some of these vulval fold infections and it could be a disease like this. Oral corticosteroids leads to faster remission, in these cases, so, this would probably be, I'd be wanting to factor this corticosteroid into the treatment plan and relapses are common, with drug tapering, so whatever you use, it's probably gonna have to be used in the long term. And with that, I'm just about on time and I want to thank you all for listening and thank webinar vet for inviting me to come and talk on this topic tonight.

John, thank you so much for that. That was absolutely fascinating. And, and, besides all the new information you've presented to us tonight, it was nice to get a new perspective on some of the drugs that we kind of use on a common basis.

So thank you very much. Really appreciate it. OK, thank you.

We do have just a couple of questions coming through. The first one comes from Pat, and it says, anything new on vitamin D for atopic dermatitis or stem cell therapy? Not, not really.

I, I, I, they have, if you look in the literature, there have been a few publications looking at, at both, but especially vitamin D. There's a few publications in Veterinary dermatology, the main journal that, that, that we see these sort of, studies published on, but nothing really that's sort of come out, conclusively that we would change any sort of treatment recommendations. So, in answer to the question, not really, but it is an area that has been looked at.

OK. You were talking about the, anti CCD, testing and everything else. There's somebody's put a question saying which labs are, are using this at this stage?

Well, I don't, I, the honest answer is I don't know all of them, but I know that IEX have just started to, well, recently, relatively recently have started to do this. So if you do an IDEX serology report, you'll see that mentioned at the bottom. I also know Bats lab, have been doing this for some time, so those are two that I do know do it, but, but beyond that I, I don't know them all because I, it's it's impossible to sort of.

Track, track them all I'm afraid. You know the ones that you use. Yeah.

There is a comment here from Arthur that says, I find you can use cyto point as and when pruritus occurs, sometimes as much as 14 weeks between treatments. Yeah. Yeah, well, that's, that's a good, good point.

And I guess, because it has such a quick onset of action, I think it, it is one of those sort of drugs that you probably can use reactively in some cases. And certainly although there's this licence to use it every 4 weeks, . There there is certainly a feeling amongst people that use it, that in many dogs you can extend that time out, which obviously reduces the cost, reduces the visits to the vet.

14 weeks is impressive, so I personally haven't had such a long interval, but, but certainly, yeah, I mean there's, I don't see any reason, for, for not doing that. The only downside perhaps. It right would be if you allowed skin lesions to flare up to a certain point that you then might risk flare, you know, secondary infections pooping back in.

That would be my main concern in the sort of cases that I see, but I guess if you were very quick to act on it, then, that's, yeah, that's quite a good way of dealing with it. I suppose it also a lot of that depends on, on the owners. Certain owners would, you know, pick up things that literally the drop of a hat, whereas others would be, oh yeah, no, it's been there for a while now.

Absolutely, and if you've got a really diligent owner, I think that, that, that, that plan could work very well. Yeah. Sue's asking, she has a dog that has recovered from dermaticosis that was treated with proveto, but it has ongoing medium to intense pruritus.

What would be the safest antipyretic drug to use in these cases? And she mentions that costs are an issue. OK.

Well, I mean, I, I suppose, I, I suppose. We don't really, I suppose you don't really know what, I don't really know what's causing that pits, I should say. So is, is that, are we, are we dealing with a dog, for example, that might have underlying allergic skin disease as well, if that's the case, then I suppose of the licenced ones, then normally I must, I must admit I'd be wanting to reach for something like cytopoint or trying the allergen serology or intradermal testing route for immunotherapy because those two therapies would be, would be the probably the better ones, for a dog with a history like that.

But if cost was really a, a, an option, an issue to the point really where you had no choice but to use something like, a corticosteroid, for example, well, I mean, it's not unheard of, to use that in a dog that's had a history of dermaticosis in, in years gone by when we used to deal with adult onset demiticosis cases that had an underlying atopic dermatitis as well sometimes. What we have to do is actually keep them on their treatment for atopic dermatitis, but just treat them for the parasite alongside it. Now if you're in this, in a dog like this one, you might keep the dog on Braveto and use corticosteroids, and probably the risk of of relapse is very low.

To my knowledge though, no one's actually looked at that because it'd be quite interesting to sort of know whether that was able to control it even with some of these other drugs. But my feeling is it probably would. Yeah, and just go with the low, very low end of the steroids to start with.

Absolutely, yeah, just always use as lower dose as possible. Always a good idea, as you say. John, that's brought us to the end of our time and the end of our, our questions.

Once again, thank you so much for your time and the information. It certainly has been, a very interesting evening of, of renewed, information and new information on top of it. So thank you for your time and we look forward to seeing you on the webinar vet again.