Thank you very much and welcome everybody to this webinar on immunotherapy. I'm going to talk about immunotherapy, in terms of what its advantages are versus the other treatment options that we have. So I will start with giving you a little introduction on ectopic dermatitis.
And then I will talk more specifically about diegen immunotherapy. And then compare it to the other treatments and what the advantages are and and then do the comparison of the various treatments looking at the efficacy, the adverse effects, and the costs of the different treatments that we have available. So what is ectopic dermatitis?
Ectopic dermatitis is a pruritic and a relapsing chronic dermatitis. We normally associate it with environmental allergens, and these environmental allergens can either be indoor allergens such as the house dust mite allergens and storage mite allergens, and also mould allergens, or they can be outdoor allergens such as grass and tree pollens, and you'll also find mould allergens outside. We mustn't forget that ectopic dermatitis can be associated with food as well, so it can be food induced.
And that would depend on whatever the individual is intolerant to as in its dietary protein. It may be intolerant to additives or preservatives, but the preservatives and the additive factors are not very well known as yet. So ectopic dermatitis is a multifactorial condition which is influenced by a whole lot of different things, and the level of prurituss will depend on several factors.
So for example, higher the allergen load, the worse the clinical signs will be because there will be increased exposure to the allergens. Also just The allergens will vary with the seasons. So for example, in the summer months, we will have a high allergen load if an individual is allergic to both grass pollens and also indoor allergens like the house dust mite allergens.
We know that utopic dogs suffer a lot with infections, in particularly bacterial and yeast infections such as malathcasia, and this can increase the level of prurituss really quite considerably. In addition to that, pruritus can result from dermatosis and sarcotic mange, and these are the two things that we need to be aware of, not just before making the diagnosis of ectopic dermatitis, but also during the management of ectopic dermatitis. Some dogs have a genetic predisposition or susceptibility to developing utopic dermatitis, so we need to be aware of this.
And itopic dogs will require long term management. So in order to make this treatment successful, we need to make sure that the owner understands the condition, and this does take quite a lot of time to explain to the owner, and quite often it makes it easier if we compare it to either hay fever or to asthma. The success of the management will depend on also how committed the owner is and what sort of compliance we will get during this management process.
And we have to also remember that not all the pets respond to the treatment. In the same way, so some dogs will respond to some treatments and other dogs won't respond. So we have to make sure that with ectopic dogs we need to individualise the treatment and tailor it to suit both the pet and the owner.
So ectopic dermatitis is a clinical diagnosis, and based on a systemic review that looked at the publications. Which were based on the diagnostic criteria used to making this clinical diagnosis, Favreau in 2010 came up with The set of clinical criteria that I've listed out here, they include the age of onset. And this must be under the age of 3.
So for example, if we have a dog that comes to us at the age of 11, with never having had a skin disease before, then it is unlikely that that dog actually has utopic dermatitis. Most of the dogs that do suffer with at atopic dermatitis tend to be indoor dogs, and most of them are glucocorticoid responsive. Many of the dogs that we see in general practise also will have recurrent bacterial and more recurrent yeast infections.
Quite often these dogs will have recurrent otitis as well. These dogs will show lesions on their feet, as you can see here in my two pictures in the digital and also pedal erythema and alopecia. Generally the ear margins are not affected, but the pinnae are affected on the concave aspects, that is the medial aspects of the pinnae, and generally the lumbosacral areas are not affected.
So once we've made that final diagnosis of ectopic dermatitis, we then look at the treatment options that we have. These options that we will come up with will depend very much on whether the condition is seasonal or whether it's non-seasonal. It will also depend on the severity of the lesions and also whether this condition is acute or chronic, and I'll talk about that a little bit more detail as I go along.
And based on on these these factors, we will then have a series of treatments that we can look at. We can look at allergy and immunotherapy. We also have a number of pharmacotherapeutic drugs that are available to us that we can use for the management of this condition.
We can put in avoidance measures, and we can look at the various other supplements like the nutraceuticals that we have in order to To help these dogs with the condition. What we do need to remember is that ectopic dermatitis is a lifelong condition with no cure, and therefore lifelong management is required for these cases. So the approach to the management of ectopic dermatitis can be divided into two, and this is how I do it.
I have proactive treatment and reactive treatment. The proactive treatment forms the basis of having in place. A protocol that will eliminate the problem before it happens.
And in this case, or in case of ectopic dogs, it is to stop the pruritus and the erythema before it happens. And we can do this in a number of ways. We can look at managing the epidermal barrier, and I'll talk about this again in a little bit more detail.
We can manage the immune responses. And then we have the various drugs that will keep the prurituss under control should we need to use them. We can manage the allergen load and exposure once we know what the dog is allergic to, and we should manage the flare factors with the regular bathing so that we manage infections, etc.
And then the second part of this management approach is making sure that we train our clients to go for reactive treatment. So we stop the event from progressing. So we're as soon as the prris happens, so as soon as there is erythema, we start intervening using some of the treatment options that we have.
In some cases where the dogs come to us much, much later on in the progression of in the process of the disease, we might have some lianification and chronic changes to the skin, which we also need to be looking at. So these are the two bases that we can start off with. So how do we target our treatments?
Ectopic dermatitis is a complex disease and it has multiple pathways in as far as the pathogenesis is concerned. In the early stages of the disease, there is a TH2 predominant. Cytokines over the TH1 cytokines, and we can try and balance this out using immunomodulation, using immunotherapy.
We also know that the allergens penetrate through a disrupted epidermal barrier and are exposed to the immune system. So if we maintain the epidermal barrier using essential fatty acids and ceramides, etc. Hopefully, that will improve or help manage these dogs longer term by improving the court condition.
Once the allergens are exposed to the immune system or the skin immune system, then we get a cascade of inflammatory cells being pulled into the skin. And in order to manage the inflammation induced by the inflammatory cells, we have a series of drugs that we can use. These include glucocorticoids, calcium urine inhibitors, such as cyclosporin.
We can use phosphodierase inhibitors and also aides. And in this group, we can also consider using antihistamines, but their value is actually not very well, . Regarded at this present time because we have a lot of better drugs on the market.
And For us, the latest drugs target into leukin 31, the cytokine that is involved with pruritus, and for this we have occitinib, which is a Jack inhibitor, and we have Loyvetab, which is cytokine, which is a monoclonal antibody. So taking these targets into consideration, we can see how we can use them proactively to prevent the clinical signs that is needed to deal with the pruritus. So here I have a Westie that is being managed well, and is in remission.
With immunotherapy, but in order to maintain this dog in this sort of state, it needs a multimodal approach. You would need to use additional things like the essential fatty acids, make sure there is good flea control. There's regular bathing, and also the avoidance measures are in place.
Then the next set of dogs that we might see, and these are the ones that are really easy to deal with, they are those dogs that have this acute reaction, so they come to you with bright and erythema, as you can see in this picture here. And these dogs need something that is fast acting, and for this, we can look at Dry blocky and systemic glucocorticoids. Then we have those dogs that come to us in our clinical practises which look like this Westie in this last picture here where the skin is really like canified and hyperpigmented and there are lots of secondary infections going on.
And in these cases, we would need to deal with the secondary infections. We would then need to also deal with the pruritus, and also then put in place all the management options that we have in order to control these dogs. So one of the most useful proactive treatments that we have for managing utopic dogs is allergen immunotherapy.
It is the only specific preventative measure to modulate the immune response. It However, requires identification of the allergens. It is a safe, long-term treatment, and it is a treatment that can be administered by the owners.
It can be used concurrently with other symptomatic treatments and in the long term, it may also reduce the usage of the symptomatic treatment that we have to use. And in some cases, it might even offer a cure, but I will talk about that again as well. And it is.
When we look at it, a fairly cost effective treatment. So the success of allergen immunotherapy. Depends not only managing the flare factors, but also on the allergen selection, which I will talk in a little bit more detail in my next slide.
But It also have to we also have to remember that it can take several weeks to months to take effect. Where it can take effect, it is thought to be effective in up to 80% of dogs and as little as 50%, depending on the publication that you read. It has a It's mode of action on various T cell responses.
So it will affect the Langerhan cells and the TH1 and the TH2 cells. So allergen immunotherapy, the affects the T cells and the B cell responses. It is also associated with the production of IgG blocking antibodies, and it is also known to increase.
The deregulatory cells, there is increasing evidence now to say that the allergen immunotherapy effect depends on increasing deregulatory cells, which helps rebalance the TH2 and the TH1 immune responses. So it basically shifts the TH2 response that we see that predominates in ectopic dogs towards the TH1 immune response. There are various formulations of allergen immunotherapy available in the UK and one of the ones that we commonly use is the subcutaneous injectable form.
This itself comes with different formulations. It can be an aqueous formulation, which is given as a more frequent injection and it is absorbed faster. Or it can be available as an all precipitated formulation, which needs less frequent injections and it is more slowly absorbed.
The LM precipitated formulation, the injections are given over weeks, and the one for the Areous formulation are given over days. Generally, the protocols are given to us by the laboratory or the manufacturer of the immunotherapy, and in general, it is divided into an induction phase, which basically means you're giving it depending on the aqueous or the allen precipitated formulation over days and weeks, . Or it can be given as a rushed immunotherapy.
But if you're doing the rushed form of immunotherapy, the animal would need to be hospitalised because this is done over hours. The once the induction phase is over, which usually on average lasts about 3 months, you then go on to the maintenance . Dosing, which is generally every 4 weeks.
However, this can be tailored. To the individual needs once you have established a pattern of when the pruritus relapses, so in some dogs you might find that the pruritus relapses at 2 weeks, in which case you might increase the frequency of injections every 2 weeks. In some dogs, when the allergen load is low, for example, in the winter, you might be able to extend that injection right up to 6 weeks, but it will really, really need to depend on the individual, and these can be tweaked to the needs as as time goes on.
So for the subcutaneous immunotherapy. The adverse reactions or the adverse effects that we might see include an increased edge. For 1 to 2 days after the injection.
And sometimes they might develop a small swelling at the site of injection. It is very rarely that you will see inflexes. However, it is good practise during the induction phase to ask the owner to wait in the clinic for about 30 minutes during the first few injections so that we avoid that or minimise that risk of the OA going home and then having to come back because it's reacted adversely.
The only time I have seen an adverse reaction to immunotherapy was when I was doing an intradermal test, and touch wood, I've not seen it during the course of the actual therapy itself. For those dogs that might show an increased edge for a day or two, you can consider giving it an antihistamine such as hydroxyzine on the day before. The day of and the day after the injection to help reduce it or now you can use lacitinib or prednisolone.
I will frequently give them antihistamines because I feel that they are relatively easy to use and most people associate good response with the hydroxyzine that I give them. The other formulation that we have for immunotherapy is the oral mucosal formulation. And this used to be referred as the sublingual immunotherapy.
This is administered in the oral pouch as drops using a pump, and it has glycerol in it for stability. Most of the formulations that we have can be administered as a twice daily therapy. A veteran has recently brought out the oral mucosal therapy that can be given once a day.
This often is an issue with some of the clients because they don't like administering medication every day into the pouch, so this might be less favourable for some clients compared to the subcutaneous formulation. There is suggestion, however, that some dogs will respond better to the oral formulation than when the injectable formulation has failed. The adverse reactions with the oral formulation or the sublingual therapy is facial pitis or local.
Edoema of the face. So to do immunotherapy, we need to identify the allergens that are involved and we can do this using an intradermal allergy test or we can do serum allergy testing. Now the serum allergy testing will depend on the laboratory.
They may use monoclonal antibodies. They may use polyclonal antibodies, or they may use the FC epsilon receptor based test, which is Supposed to be more accurate. And one thing we have to remember about the serum allergy test is that this is an indirect measurement of what is actually going on in the skin.
We can use the information that we get from allergy testing to reduce the allergen load, and also to reduce the allergen exposure and also to formulate that immunotherapy. So, what we need to remember is that allergy testing is only for the IGE mediated disease. And this can be identified using intradermal allergy test or serum allergy testing.
Here on the picture here I've shown you. An intradermal test where there is a will and fair reaction and you can see a number of reactions in this particular dog. And there is a a test on the it's a test result from the serum allergy test on the next slide, on the next side rather.
So What we also need to bear in mind when we are doing allergy testing is that we can get false positive and false negative reactions and certain medications. Can also affect these test results. It may be that the allergens that are in the animal's environment are not in the standard allergen testing kits, and we also have to remember that not all ectopic dogs have an antibody mediated disease.
So we have dogs that present with exactly all the clinical signs that we see in. In atopic, truly atopic dogs, but when we test them both with intradermal testing and with the serum allergy testing, they are negative and we refer to these dogs as having opic like dermatitis. We also know that the age can influence the allergy testing results.
So if we test the dogs when they're very young, and generally I don't test them under the age of 12 months as there is an increased risk of getting a false negative result. I talked about seasons earlier and seasons can also influence the allergy test results. So for example, if we're looking at a dog that has pollen allergies, so this dog shows clinical signs in the summer months, then the best time to test that dog is at the end of the pollen season and not in January because there are no pollens in January, certainly not in the UK.
Recently, IgE against cross reactive carbohydrate determinants that are found on insect and pollen allergens, have been found to result in a false negative reaction on serum testing. There are some laboratories now, such as RU that actually offer tests that will block these antibodies, so we get less false positive reactions. Sometimes we will get borderline results, and what do they mean?
So we have to then look at correlating these results that we have with what is going on in the animal's environment and other things. So this correlation that we look for allergies, allergen selection for the allergen immunotherapy. Has to be correlated between the history and the clinical signs and whatever the allergens have shown up.
So an example of this is, if we have a dog with non-seasonal disease that shows Positive reactions to pollens alone, then we have to question it because this dog has clinical signs in the winter months and we're only getting a results showing pollen allergens, and clearly this dog is allergic to other things as well. Similarly, if we have a dog that shows positive reaction to or positive IG to guinea pig dander, then we have to question this if there is no guinea pig in that dog's environment. And never really comes into contact with it.
The timing of the allergens is also important. So for pollen allergens, the best time to test these dogs is at the end of the pollen season in order to get the highest level of pollen allergen IgE that we are looking for. So it is often very difficult to assess the immunotherapy efficacy, but, but it can be demonstrated by either resolution or mark reduction in the clinical signs, that is a reduction in the pruritus and all the other signs of itopic dermatitis.
So for example, those dogs that have recurrent pyermas maybe we'll see them less frequently with the recurring pyerma. In some dogs we will see a reduction in the need for the symptomatic treatments that they might need at the same time. There are studies that use vast or visual analogue scoring methods in order to assess the efficacy of immunotherapy, but generally in practise I find that the clients get terribly bored with this because the response time can take up to 12 months for us to see a pattern as to how this dog is responding.
And because it takes this length of time to judge the efficacy of immunotherapy, we should allow at least 10 months and preferably 12 months before discarding it as a management option. One thing that I often get is People or practitioners thinking that we cannot use concurrent treatment. We can use concurrent treatment without an immunotherapy.
Certainly in the induction phase, it is very useful. It reduces the pruritus and the clinical signs and then. As these improve, we can either start tapering it off and ceasing it completely during the maintenance phase to see whether the dog can come off completely from the from the symptomatic treatment, or whether we might need to continue with it but at a lower level.
There are a number of factors that will influence the outcome of allergen immunotherapy. They include infections, and if we actually identify the infections and treat them at the early stage or prevent infections, then we will have better outcomes with immunotherapy. Often the dogs that go on immunotherapy won't respond just to immunotherapy if there are chronic changes in the skin.
I have mentioned the selection of immunotherapy, so if the allergen is present in the dog's environment, then we're likely to get a better response. But if the allergen is not present in the dog's environment, then obviously the response rate isn't going to be as good. So this will be poor allergen selection giving us poor efficacy.
The older animals that come to us may have a reduced response rate. And then we also have to remember that we can have cross reactions between environmental allergens and also dietary allergens, which can result in relapses and that can appear as an ineffective treatment. So we're still looking at in part the proactive management, and this is something that I will use commonly together with my immunotherapy, and these are things that we do to maintain or improve the epidermal barrier.
And we can do this by limiting the amount of allergens that will penetrate through the disruptive barrier that has been associated with the condition. We can do this in a number of ways. Bathing the dog can remove the allergens from the skin.
We can also look at doing certain things in the environment. So for dust mite allergens, vacuuming the type of bedding that we use will help for pollen allergens, we can identify the plants and make sure that the dog is not walked in the areas where the allergens are present. There are a number of products that we have available.
That can be used to restore the epidermal barrier, and I've listed a few here, and that will depend on what you have available in your practises. We can also use nutritional supplements to help the barrier function. We can use diets.
These diets are enriched with antioxidants and essential fatty acids, or we can use them just as straightforward supplements, and there are a number of these on the market. They will include omega 3, omega 6 fatty acids, vitamin C, zinc, and also vitamin D. So How do we compare immunotherapy to and where does the reactive treatment come in?
So those dogs that come to us with Acute signs of erysema and excoriations, we will tend to use a different type of treatment approach or we need to bring that pitus under control, and for this we can use drugs such as locitinib for targeted use. This has a rapid response. It can act within 4 to 12 hours of administration of the drug.
We can use it with the combined preventative measures that I've already talked about, and it may be very useful to use oxcitinib for ectopic dogs. If we are going to use oxraccitinib long term, we need to make sure that we look at the contraindications for long term management and also this will require a certain amount of care and monitoring as it is an immunomodulator. Using a case study, I will show you how I use a combination of lacetinib and immunotherapy to get the best clinical outcome.
So here are some pictures of a Jack Russell terrier. This is a dog that I saw at the age of 3 with erythema and. Pits on the ventral abdomen, on the anterior aspects of the elbows, the peroral areas, and the axilla.
And this is the typical site at which we will see the clinical signs. So for a typical skin workup, we always do skin scrapes to rule out parasites. We will rule in or rule out microbial infections, whether they be bacteria or yeast infections, and and then look at the role of food, whether there is an element of cutaneous adverse food reaction as well.
In this case for Rosie, all this was done, and then an intradermal test was carried out. She showed positive reactions in the top row here. You can see the first one here is the histamine control.
The 1st 3 here are storage in house dust mite, and in the second row here are pollen allergens, which are grass pollens, and they are markedly increased and positive. So for a case like this, for the acute flare, in this case I used an antibacterial anti-fungal shampoo, although there was no infection there, when we have pruritus, you might get micro trauma and you might get secondary infection setting in. To control the pruritus, I used acitinib for 2 weeks at the twice a day treatment and for 4 weeks once a day.
And based on the allergy test result or the intradermal test result, immunotherapy was prescribed as a proactive measurement or a preventative measure, rather, and an oatmeal based shampoo for managing the Brightest long term, and she was also put on essential fatty acids. The owner was prescribed alacitinib to give the dog tablets for 3 to 5 days at the onset of pitus to break the itch scratch cycle because we know that ectopic dogs will have flares at some point or another, and if we can break this cycle early on, then our dogs on immunotherapy tend to respond much better. So here's the pictures of Rosy pre and post short term treatment here are the before and here are the after.
Rosie is now being maintained on immunotherapy and she does get short courses of locitinib in the summer months. In order to break the itch scratch cycle when the pollen allergens are present and you tend to get those flares when the allergen load exceeds the threshold. So for these dogs, we also want to look at the advantages of shampoo treatment in managing these dogs with ectopic dermatitis.
It reduces the pruritus. It reduces the inflammation and the allergen load, and it also removes any microbial organisms and helps moisturise the skin at the same time. Which shampoo we choose to use to manage dogs does need to be individualised.
If you're looking for a shampoo that just is needed for pruritus, then you can consider using a colloidal oatmeal shampoo, or you can use an antibacterial anti-fungal shampoo if that is what is indicated. So we then look at the other options that we have. We can look at LovetMap, which is the monoclonal antibody that we have cytopoint.
It targets interleukin 31 and in talks with atopic dermatitis, interleukin 31 was found to be at increased levels in the serum and the skin. And if we remove this by binding it to the Monoclonal antibody, it reduces the levels and thus the pits. In the UK Locuvetabb is licenced at 1 milligramme per kilogramme every 4 weeks, and it can be used with concurrent medications.
The adverse effects that they did report are mainly vomiting and diarrhoea, but when they looked at the clinical trials and the study results, there was not a lot of difference between the placebo and the treatment groups and As far as the monitoring concerned, there were no haematological and biochemical differences between the placebo controlled and the treatment groups. We often use glucocorticoids. These are very fast acting, and they are broad targets, so they will target a number of different areas of that pathogenic pathway.
They will affect the inflammatory cells. They will affect the human immunity, cellular immunity, and also reduce the vascular permeability. So we have less edoema, and this is where steroids come in very useful when we're looking at ear disease.
So talk a little bit more detail about the steroids that are available for us. They include the topical glucocorticoids, so for example, hydrocortisone ainate, which is cordovans, which is very useful, and also sometimes we will use is that is that contains betamethasone. Hydrocortisoneociinate was shown to be very useful in one particular double blinded placebo control study where they treated 41 dogs daily for 7 days and then twice daily.
They found that the dogs in the treatment group. On average had a flare up at about 113 days. Whereas the dogs in the placebo control group had flare-ups on average about 30 days, so clearly the hydrocortisone oipinate as a proactive treatment is useful in managing these dogs.
However, we need to remember that even topical steroids that are Used on the skin alone can have adverse effects as you can see on this picture here. There's a lot of thinning of the skin and these yellow crusts here are actually areas of calcinosis. There is a lot of thinning of the skin.
Many of us in practise will also consider using as our first line treatment prednisolone and using prednisolone or methylprednisolone to break the itch scratch cycle for short courses is very, very useful as long as we don't have any best effects, we should use this at the lowest, dose that we possibly can and on alternate days and minimise the amount of steroids that we use. The clinical adverse effects that we see in the early stages include the polyuria, polydipsia, and polyphagia. Sometimes we will have as we go on, other adverse effects, and in particular when we're using glucocorticoids longer term, then we may get things like recurrent yermas, dermaticosis, and icrogenic Cushing's.
Another topical treatment that can be quite useful as a proactive treatment is tacrolimus. This can be used in localised lesions. It is well tolerated and it has the advantage that it is of a low molecular weight and penetrates through inflamed skin.
Here is a golden skin of a golden retriever with the areas on the thorax where it would get these recurrent erythematous lesions and tacrolimus is quite useful for something like that, and it is also very useful for those dogs that recurring interdigital systems that you can treat topically to help these dogs. So I mentioned that in some cases we do get dogs presented to us with more chronic lesions that are hyperpigmented and like any fight and have microbial infections, and typically we may for these dogs have to look at Both reactive and proactive treatments, and I will again, the principle is the same. So you reduce inflammation, reduce pruritus, but we have to reverse those chronic changes that are present within the skin and and then look at how we're going to maintain these dogs to prevent flare-ups.
And I will demonstrate this. To you, using a case study. So here I'll talk about in West Island terrier that was referred to me at the age of 11, which was not responding particularly well to occitinib and was referred for immunotherapy.
It had a free trial with. Not respond, had not responded to it. Skin scrapes were negative and it was positive on tape strips, positive for malahesia and also bacterial overgrowth, syndrome.
So this is the dog here and here are some close up pictures of this particular West. You can see the severe thickening, scaling lianification, hyperpigmentation on the ventral abdomen, axilla extending right down into the legs, and this is the ventral neck, and here's a close up of the neck. So the treatment and management plan for a case like this would be to deal with the microbial infections and in this case 2% chlorhexidine, 2% myanzole shampoo was used, which is malab.
Systemic antibiotics were given for 6 weeks, and the otitis was treated with automax. The management for pruritus was started after we get negative cytology for bacteria and malasthesia, and in this case, the reverse of chronic changes, prednisolone was prescribed at 0.5 mg per kilogramme once a day for 10 days and then every other day.
In addition, all the other proactive measures were put in place as well. Which included improving the epidermal barrier, washing the dog regularly, and also using an air cleaner regularly. So as you can see from these pictures, there's a marked improvement in the skin.
So you can see there's a marked improvement in in the lichnification and the hyperpigmentation, although there are some Changes here, but you will also note that this dog now has a pop bellied appearance. It is beginning to show signs of polyuria, polyphagia, polydipsia, and so this is the time which should alert us that we need to change the treatment here. So this takes me on to a longer term treatment of managing ectopic dermatitis with cyclosporin.
So in this case, the Westie was put onto cyclosporin and this is the dog 6 months later. So This takes me on to how cyclosporin can be used. This is a drug that has multiple targets, so we refer to it as a drug with broad targets, works on the T helper cells, cytotoxic T cells, Langerhans cells, macrophages, monocytes, eucino cells, and also mast cells.
So, it has a place, cyclosporin has a place in managing these ectopic dogs. In the systemic review of several clinical trials on cyclosporin, it was shown to be effective in reducing pruritus and also reducing the lesion scores in many of the dogs that we treat. The key with this is to, again, reduce the dose to every alternate days, depending on the clinical response.
The main thing with the use of cyclosporin is that it takes several Days or more like weeks to kick in, so it will take between 3 and 4 weeks to kick in. And so in those drugs when we want to stop that, we may need to combine it with a fast acting drug like glucocorticoid or latinib for approximately 3 weeks. As far as the cyclosporin is concerned, we need to be aware of the adverse effects.
So many of the dogs and in this clinical review, systematic review that they did, gastrointestinal signs were the most common. About 40% or more than 40% of the dogs showed. Gastroenteric signs.
In addition to that, we get dogs with papillomas, hyperplasia, hyperplastic. Gingival hyperplasia, hypertrichosis, so those dogs that we normally would clip it every 8 to 12 weeks, mainly clipping every 6 to 8 weeks, and then we have to be aware that this is an immunomodulator, and so. Pymas and malathesias infections need to be looked out for.
So this brings me back to allergen immunotherapy and so . In Summary, the advantages of immunotherapy over the other drugs are that we if we're using. Subcutaneous immunotherapy, we can give it as a monthly treatment, and it is less labour intensive.
It has no risk long term use. And it can alter the course of the disease. And in some dogs, you might even get a cure.
It is a cost effective treatment. It can be used as a preventative treatment, and it doesn't require long term monitoring. The disadvantages of allergen immunotherapy are you and really in my opinion not very significant except in dogs that don't tolerate injections.
There is that minor minor minor risk of anaphylaxis, needle injuries if the owners are doing the injections themselves. And client education is important, and if the clients are not willing to tweak the injection, sometimes you find that it's not very useful. The initial cost may be high because of the cost of allergy testing, but overall, the advantages outweigh the disadvantages.
So here I put up a comparison of the different modalities. So immunotherapy or glacinib are comparable in terms of efficacy. If you look at the top level of efficacy of immunotherapy in one of the publications.
But again, this will depend on the publication and what they were actually looking at. . On average, 2/3 of the dogs will benefit from immunotherapy.
We know glucocorticoids will help mostly old dogs. But then we have to look at what, how frequently we give them. So immunotherapy is less labour intensive.
Otinib needs to be given daily, glucocorticoids on alternate days, and Love map on monthly injections, but then that is expensive and we don't know about whether that does need monitoring or not. Glucocorticoids will need monitoring. Olacitinib will require monitoring, and dogs on cyclosporin will also require monitoring.
When we're using drugs on a daily basis or alternate day basis other than glucocorticoids, this can be fairly expensive for the client to to to use, especially when the insurance . Cover runs out. So, These are the comparisons, and with that, I would like to thank this latest educational website for some of the illustrations that I've used for this presentation and thank you for your attention.
Anita, that was an amazing amount of incredibly helpful information. So thank you for your time with us and thank you for sharing this with us. You're welcome.
I have. Yes, we have a question and it's come through from Arthur, and he's asked, does the placebo effect work in dogs? Because he says he has, with reluctance used Piriton in desperation after full workups, and he's found sometimes a very good response.
There could be a placebo effect, but it is more like that the Puritton has worked for the dog. And so if we look at the allergen pathway, if we use an and I will frequently Use an antihistamine in some dogs combined with immunotherapy, or I used to before we had the joy of alocitinib. And basically, if we prevent mast cell degranulation, it will prevent the histamine release and and then the cascade going down.
So therefore, it is likely that if you are giving the peritone before the the reaction happens, then it is likely to work. So whether it's entirely a placebo effect or whether it is acting as a proactive drug, I think it would more likely be acting as a proactive drug. OK.
And many years ago there was a theory which a lot of people still subscribe to that antihistamines have a, a strong cortisone sparing effect because they supposedly enhance the effect. Would you say it does not maybe directly that the drug becomes stronger, but because the the two act together much better? Yes, so basically the steroid sparing effect is that it it allows you to use less glucocorticoids.
So if part of that itch or part of that. Sorry, if the antihistamine is preventing the m cell degranulation, it may well allow you to reduce your steroid dose, for example, and I think that's where the effect was so it was before we knew the details on the pathogenesis of. It will be dermatitis.
We were, we were doing all these treatments, and since we know the pathways, we can maybe look at why, why it is likely to work in certain situations. So I don't throw antihistamines out entirely. I will still look and one of the antihistamines that I will use quite often is hydroxyzine, which is Arax.
And that that does in my experience. Reduce some of the need for glucocorticoids or cyclosporin or even opcitinib, but as my baseline treatment, most utopic dogs are on immunotherapy. OK.
You, you've actually answered our next question. Tara wanted to know what was your favourite antihistamine and do you find that there are varying effects between them on dogs? So yes, there are varying effects and based on the pharmaccokinetics and dynamics, the only antihistamine that we have any data on is hydroxyzine, and that would be being given at 1 to 2 milligrammes per kilogramme every 8 to 12 hours.
OK. But I suppose it's, it's possible that some of the others are going to work in certain circumstances. It's just, you know, it's like a bit like anaesthetics.
What's the best anaesthetic, you're comfortable with the one that works for you. Yes, and, and it depends. So sometimes owners what we find is that owners will have certain things in their, in their drawers, shall we say, .
Because they, they are asthmatic or they suffer from hay fever, and if you ask them what they have and if they can use that straight away, you know, at the early phase, then it prevents that itch scratch cycle, stops that progression of the disease, and I think that is really useful. It stops those dogs getting to us with that like. And hyperpigmentation, which in itself can be so difficult to reverse.
Yeah, yeah. I think the term you were looking for there was home pharmacy. Some of them were well.
Oh yeah, OK. Anita, Sue wants to know, are any of these drugs OK to use in very pruritic Demodex cases? The only, so, if you have Demodex, the Dematex can cause, in itself cause pruritus, the one, if I was going to use, I would use an antihistamine until I cleared up the Demodex and then see what I was left with and then go from there.
Excellent, excellent. Anita, as I said, this has been some very useful and valuable information and I really would like to thank you for your time tonight and thank you for persevering when we had to get you through all the technical challenges to start. I'm sorry it didn't work today.
It did work when we did the trial run, but this is the nature of technology, I'm afraid. Murphy's law, but in the end and I'm the attendees you persevering. So thank you for your time tonight.
OK, you're welcome. I think the problem has been that there are a lot of people streaming Netflix and stuff like that. I think you're right.
I think you're right. Folks, that's it for tonight. Thank you for your attendance and I hope you've got some valuable information out of this.
To dawn, my controller in the background, thank you for all your help earlier and from myself, Bruce Stevenson, it's good night.
