Hello, thanks for joining us. Welcome to this webinar on the diagnosis and management of chronic enteropathies. For me, this is always one of the greatest topics to to lecture on because I think it's a case presentation that many of us spend a lot of time seeing.

And so having a logical approach to these is a really useful thing for us to have. My name is Andy Kent, I'm the clinical director and a medicine specialist at a new referral centre that's opening a little bit later this year in in November called Blaze, which is gonna be just on the kind of southern tip of Birmingham. So if you're in our area, then hopefully you've heard of us.

If you do have any questions on the back of this, this webinar, always delighted to hear about cases or be contacted with any queries so you can see my email address there on the screen. So what are we gonna cover today? Well, really we're gonna try and give you a a practical approach to to seeing and dealing with dogs and cats with chronic gut disease.

So we'll talk a bit about the history and the things we might think about when we're talking to these patients for the first time. We'll look at those clinical signs and then we'll go through that kind of diagnostic algorithm and talk about how we're gonna treat those at the end. So hopefully it's a little bit of a rundown of everything.

So what do we mean by chronic enteropathy? Well, generally we're gonna be referring to chronic gastrointestinal signs, vomiting, diarrhoea, those kind of things. How long do they have to be going on before we consider them chronic?

Well, if you look in the, the literature of these things, I suppose we would generally consider that those are signs that have been present for greater than 3 weeks. Now that's quite a long time in some situations, so I suppose we don't always leave it that long, but we do need to be mindful of the fact that. Acute gastrointestinal signs are relatively common in our patients and usually are self-limiting without us doing much about it.

So these have to be things that have been present for a while, I suppose. More challenging, of course, having repeated episodes rather than necessarily continuous signs, but it can be a little bit of a mixture of the two. What are those clinical signs?

Well, exactly the things that you're expecting really. So the majority of dogs and cats with chronic entroopathy present with chronic diarrhoea, #1 sign for us to be considering. Vomiting then, the second most common sign, and we see that in in some of our patients as well, and of course we need to distinguish that from regurgitation.

And then we see some of these other signs alongside that, so changes in appetite, weight loss, you know, things like that. And I suppose those can be the hallmarks of more severe gut diseases. If we think about kind of clinical severity scoring and things like that that we'll talk about a little bit later on.

You know, it is of course a more severe presentation if you're seeing animals who are inappetent or have lost significant amounts of weight. You've probably seen these from time to time and again they've kind of gained interest in terms of having a repeatable way of evaluating the, the quality of stool. But, you know, most of the dogs that we see are of course going to be at the higher end of these kind of faecal scoring charts, so it's usually dogs who consistently are at a kind of 6 or 7.

Now it helps us when we're thinking about gut disease to try and localise that disease, and I'm probably teaching you to suck eggs a little bit in this, but it's important for us to try and work out whether these are small intestinal or large intestinal signs. So for those of you that are not thinking about this routinely. Generally for large intestinal disease, we're talking about colitis type signs, aren't we?

We tend to see stool that may have blood or mucus, there's straining, so tinesmus, and often smaller volumes but markedly increased frequency. These are dogs who go very, very regularly. Small intestinal diarrhoea, the opposite of that, often larger volumes.

The frequency may be up a little bit but not dramatically so, but very commonly associated with other signs such as vomiting, weight loss, you know, malabsorbative type processes. The reason that we think about that is because of course that helps us in terms of them knowing where we need to look with our investigations. If we see dogs with colitis and we start looking at the stomach and the small intestine.

Of course we're unlikely to explain those signs, and our approach to those is sometimes a little bit different. Our nutritional approach, for example, between small and large intestinal disease may be different when we consider things like the addition of fibre to diets. So worth thinking about that when we're taking history from our patients so that we understand what may or may not be going on.

One of the things I always flag as well when it comes to history taking in dogs with gut disease is to try and think about whether there are any clinical signs that are perhaps unusual in dogs with a a typical inflammatory enteropathy. Most dogs, the majority of dogs that we see are often well dogs with, with gut disease, you know, well dogs with diarrhoea or vomiting. Although of course there are more severe manifestations of these diseases with protein losing andropathies, for example.

But we don't tend to see, you know, significantly altered mentation, PUPD, you know, so they're not always or often that. Unwell, these kind of patients. So if you have dogs who are very unwell or who have unexpected signs, it should perhaps prompt us to consider whether actually these gastrointestinal signs might be a manifestation of a non-gastrointestinal disease rather than a gastrointestinal disease.

And that's of course an important thing for us to exclude in our differentials. Abdominal pain is maybe a bit of a controversial one, but I think your typical dogs with a chronic entroathy don't have significant abdominal pain. Maybe some of them can get some concurrent motility disease, for example, but you know, it's not, it's not something that's evident in the majority of our patients.

So when it comes to patients who present to us with chronic gastrointestinal disease, of course one of the things we have to do early on is try to exclude those non-gastrointestinal causes, make sure that this is not just a manifestation of something else going on. How are we gonna do that? Well, often that's related to our blood work that we might think about doing early on.

So what things should we be excluding? Well. Atypical Addisons, or indeed typical Addisons, depending on what the electrolytes might be doing, is a cause of waxing and waning gastrointestinal signs, and many of us would use a basal cortisol to exclude that as part of our, our early investigations.

I think that's become standard practise in many chronic gut disease investigations. If you've got a basal cortisol that sits over 55 nans per litre, reasonable way to exclude Addisons. If you have a level below that, certainly does not mean that that is the diagnosis.

We see many dogs without without Addisons who have a basal cortisol that that sits below that level, but then we would need an ACTH stimulation test to exclude it. What about the rest of our blood work? Well, in many cases, as I said before, these are well dogs and may well have completely unremarkable blood work biochem and haematology.

What can we sometimes see? Well, maybe a slight increase in our liver enzymes and, and that can just represent in many cases a secondary hepatopathy. We expect then the liver enzyme elevations to be pretty mild.

We may see some haematological changes, we may see some other biochemical changes. I suppose the things that I'm most interested in would be what the protein levels are doing. As we mentioned before, you know, protein losing enteropathy is a more severe manifestation of chronic gut disease and something that we need to pick up on if that's the case.

It has implications in terms of prognosis, it has implications in terms of the way that we investigate that patient. So looking at where our albumin and globulin is, is very useful. And the classical pattern that we see of that would be that both the albumin and globulin tend to fall in dogs with protein losing entropathy, in contrast to something like a protein losing nephropathy, where often it would be just the albumin that might be reduced in that situation.

But ultimately we're unlikely to see anything in our biochemistry profile that gives us a very clear idea of what we're dealing with. What about CPLI? Do we routinely measure CPLI?

Well, we're not gonna get too much into pancreatitis in this lecture, it's obviously a topic in its own right, but it's worth just being aware that it has been demonstrated that CPLI elevations are present in dogs very frequently with chronic enteropathy. That doesn't mean they have pancreatitis. They may perhaps have a slightly unhappy pancreas as a result of the inflammatory gut disease.

But we do see elevations in dogs with both acute and chronic gastroenteropathies. And maybe that can have a prognostic, aspect to it. But ultimately does not necessarily mean that their gastrointestinal signs are caused by pancreatitis.

So TLI folate carbalamine, very commonly recommended tests in cats and dogs then with chronic gut disease. TLI primarily considered our kind of gold standard test for excluding EPI exocrine pancreatic insufficiency. We see that still from time to time.

We don't see so many of the, the German shepherds with the immune mediated forms of EPI as we may have once seen. We probably see more EPI now as a response to end stage chronic pancreatitis, but we still see it from from time to time. So we would generally run a TLI to exclude that as a cause in, in many of our cases with chronic diarrhoea.

And then folate and carbalamine, which are widely measured then as, in essence a marker of the function of the gut. If you're not using these routinely, folate and carbalamine are absorbed in different parts of the small intestine. So folate in the proximal small intestine, carbalamine in the distal small intestine.

And so we can use these broadly to give us an idea of how those regions of the gut are behaving. They're also important, perhaps particularly with carbalamine, because we know that deficiencies if present, can lead to reduced function of the gut. We see villous atrophy in dogs with hypocbalaminemia.

So they're both a diagnostic marker, giving us an indication of where an issue may be most predominant, but they're also an important therapeutic target. We should be supplementing carbalamine in the situation where it's low normal or below. And be careful because labs have, you know, relatively conservative reference intervals for carbalamine.

So actually just being towards the lower end of the reference range would be considered abnormal for most people. So they're a pretty vital one, I think for us to run. Undiagnosed or unsupplemented hypocbauminemia is also another reason for failure to respond to treatment.

So if you have patients in which you haven't measured this and they're not doing well with what you're trying to treat them with, it's a good thing to have a look into. So looking in at some of the other testing that we might do early on, do we routinely do faecal analysis? Well, I've got to tell you that I'm not a huge fan of faecal analysis because I think sometimes the results of these can be quite misleading.

We know that many of the things we screen for can be found in normal dogs as well as dogs with diarrhoea. And equally the role of some of them in the, the kind of causation of these diseases is unclear. Perhaps the one that I'm most interested in, in most cases would be a search for Giardia.

I think that can be a true pathogen in some situations, so either investigating for Giardia or trial treatment with fembendazole is a reasonable thing for us to do in in most of our chronic gut disease patients. What about faecal cultures? Well, really the causes that we might be interested in from an infection point of view are really things that are more likely to cause acute disease rather than chronic disease.

You know, we don't see chronic diarrhoea due to something like Campylobacter. And so routinely screening faeces for these things can be an unrewarding thing to do or end up leading us down the garden path or perhaps resulting in us treating with antimicrobials where they're not necessary. When might we think that that's more useful?

Well, perhaps in very young patients, perhaps in immunocompromised patients. And we may then, you know, have a more targeted approach to investigation in some situations. Another pathogen that is worth remembering is tritrichomonas in cats, primarily a cause of, of diarrhoea in younger cats, often pedigree cats, and that's another one where we may have a targeted approach to looking for that, so PCRing for tritrichomonas in young pedigree cats with large intestinal diarrhoea.

And this just summarises what we've just said really, that these things are present in in both normal dogs and dogs with diarrhoea. If you look at Campylobacter, for example, the isolation rates is, is almost exactly the same between diarrheic dogs and and healthy dogs. So for all of the things that we screen for both in our faecal analysis and in these extensive PCR panels that we now get offered to us, really are very challenging things for us to to look into because of the, the finding in both of these groups of dogs.

So what other tests should we think about running on our bloods or faecal samples? Well, we see lots of things, don't we, that are offered to us as perhaps being useful tools. And many of them, of course, we know are not helpful at all.

Great example of that being serum food allergy testing, which we all know is is not really a good way for us to guide things like diet trials. But there are various labs that offer us other tests with, with great claims around the things that they can do for us. Should we be using any of them?

Well, there's lots of things we can request in, in this way. So, in Texas they would offer us alpha one protease inhibitor, which is an earlier test. For protein losing entropathy tends to be positive prior to, albumin falling significantly.

So they've used it in some of the breeds who might be genetically predisposed to PLE. The problem for us, it's not hugely practical for us to get samples to them to run, so it's probably not, not commonly done. Viral testing, you know, a bit of experimental work, looking at novel viruses in, in kind of chronic gut disease, but nothing that we're gonna be running routinely.

Calprotectin or other markers of inflammation in in humans that are useful in investigation of gut disease. There's work around some of these, but I think nothing that we're going to kind of routinely advocate. You may have also seen that one of the labs, Antech has launched this canine er chronic enteropathy IBD assay.

That's really a, a kind of combination of biomarkers that they offer great claims about as being a useful test. For me, there's little evidence to support us using that at this time. The studies that that, assay was then based on.

Really demonstrated that it was only useful to differentiate dogs that could easily be differentiated in other ways. I it differentiated dogs that had diarrhoea from dogs that did not have diarrhoea. Really what we need those assays to explore is.

Or whether we can use them to look at the different forms of disease, you know, whether they will differentiate dogs with lymphoma from dogs who have a a chronic entroopathy that's inflammatory, for example. So I don't think any of these are things that we would routinely be using yet. So once we've done our blood work and, you know, we've seen that maybe we've got a slightly low B12 or a slightly low folate, maybe the proteins are a little bit low, what's our next step likely to be in the way of investigation?

Well, I suppose for most of us we might think about some form of abdominal imaging. Maybe radiographs, although we know that the, you know, the sensitivity of radiographs to look at the gut is pretty poor. So unless we think that we've got an obstruction, we're probably not gonna use radiography that frequently.

Most of us are probably going to reach for abdominal ultrasound. Is that actually a useful thing for us to do? Well, that's been explored in in this study.

And the findings of that are interesting, that actually in most of the cases that we investigate, so in 66% of the dogs, ultrasound didn't really help us in terms of the, the diagnosis. And actually it was only around 15% of patients where the ultrasound examination was considered either vital or beneficial to that diagnosis. So we have to recognise that whilst ultrasound can be a useful way for us to exclude some quite significant things such as masses, for example, in many of the patients that we investigate, the ultrasound will be pretty boring or not really give us a definitive answer.

What can we investigate it with ultrasound? Well, we're generally looking at the gut, you know, the thickness, the layering, presence of ulceration, whether we see these little mucosal striations which perhaps correlate with lymphatic dilation, whether the lymph nodes are normal or abnormal, which, you know, can be something that might make us then more concerned about neoplastic disease, what the motility is like, and again, kind of ruling out complications such as as foreign bodies or interceptions. So this might be how the gut would appear in patients with a, with a chronic gut disease.

We can see that moving around here. So here's a dog with probably a slightly thickened gut wall, got these very nice mucosal striations, which, you know, as I say, the images would report to us as as suggesting that there could be some lymphatic dilation present. I hesitate to suggest that that's lymphaectasia.

It may just be some, some lymphatic dilation. And you can probably see the er ones of you with with er eagle eyes here that there's also some free fluid in this abdomen. So this may well be a protein losing entropathy patient where we've got some, some free fluid as well.

So these are the kind of changes that we see with ultrasound. Just occasionally we see something that's really gonna change what we do, i.e., there's a big mass or there's huge lymph nodes that that can offer us a possible diagnosis, or at least give us an opportunity to take some aspirants.

So where have we got to when we've perhaps finished our imaging? Well, hopefully we've got compatible clinical signs of a, of a chronic gut disease. Hopefully our physical exam is pretty unexciting or just has some, some minor changes that we might expect.

We've hopefully excluded the non-gastrointestinal causes. We've done our cortisols, we've done our blood work. We may have given a few days of fenbendazole or done some parasite screening.

We've probably run our TLI folate carbalamine, maybe we've got a slight hypocabauminemia, but nothing hugely exciting. We've probably done our ultrasound and and that doesn't show us very much or or shows us only the expected, you know, subtle changes in the wall of the gut. So we've done lots of things, we've excluded lots of non-gastrointestinal diseases, but of course we still have a, a client who's standing in front of us, having spent reasonable amounts of money by this stage, and, and asking us why does my dog still have diarrhoea?

And so we have to then explain, don't we, that, that we are likely within this spectrum that we're gonna call chronic entropathy. And that is an inflammatory disease of the gut, and probably incorporate several areas together. Some of these will be food responsive, some of them will be due to so-called dysbiosis, some of them may be due to lymphangectasia, that can be primary or secondary, and some of them will be true IBG which I guess we, we generally regard as being the dogs that require immunosuppressants, things like steroids.

Perhaps the only differential we still have to keep on the, on the table alongside this would be dogs who have neoplastic gut disease such as lymphoma can look exactly the same as an inflammatory chronic entopathy early on, although it's usually rapidly progressive, these are quite aggressive diseases, gastrointestinal lymphoma, so, you know, significant chance that those will be more unwell dogs where our inflammatory dogs may be less unwell. But of course with things like PLE there can be crossover between the two. But most of our patients are gonna fall into this kind of spectrum.

So we then start to decide how to proceed based on the severity of the disease. And in dogs who had relatively minor or moderate disease, so well dogs, chronic vomiting and diarrhoea, we're likely to take a slightly more staggered approach to dogs who have very severe disease, if you have protein losing entropathy, for example, where we may offer you intestinal biopsy early on because of that risk that you could have a lymphoma that we haven't uncovered other ways. And because you're potentially unwell, we may throw more treatments at you together.

But in most of our patients, they're gonna fall more into that mild to moderate disease activity where we might then work through those steps, you know, we give the fembenzo, we might then think about a diet trial. We used to think about antibiotic trials, and then we might think about our biopsy later on and and our immunosuppressants. Now we very much do not use antibiotics in this setting, and I think they've completely fallen out of favour and we'll talk about some of the alternatives we have for that.

But there's no real evidence that antibiotics are useful in this setting. All they do is contribute to the dysbiosis that we're hoping to get rid of as part of our therapy. So I think antibiotic trials really are are out of favour now and I wouldn't advocate the use of antibiotic trials in dogs with either acute or chronic gut diseases.

It's just not a time for us to use it. Now if we're unsure where dogs fall on that spectrum of mild, moderate, severe, there are these activity index er schemes that have been devised where we can rate the, you know, the severity of some of the changes that we see to try and give us. Idea.

These, you know, are originally kind of research tools more than anything else, but sometimes they can be helpful for us to put a number on what's going on. And of course there's something that we can repeat with time so that we can, you know, look at changes in activity index over time. So if we take out the antibiotic trials, which of course we've done, this is how our approach is going to look based on that severity.

In the mild to moderate, we look through these therapeutic trials. In the more severely affected dogs, we may consider biopsy early on. I'd say the primary reason behind that, to exclude lymphoma, gastrointestinal lymphoma that we may not have picked up in any other way.

So let's look at some of those therapeutic trials in more detail, and of course one of the most useful tools that we have in our arsenal is to look at the diet trial. And this is a hugely useful thing for us to do. We know that it resolves the gastrointestinal signs in the majority of the patients that we see, and the younger the dog is, the higher the probability that they're going to respond to a diet trial.

What are the appropriate diet trials for us to use? Well, we have lots of choices, don't we? And I suppose we try to pick this based on a dietary history.

And that's become really challenging. Many of the dogs and cats that we see have had lots of weird and wonderful diets based on lots of different protein sources. And so trying to find a truly novel protein diet has become quite a, quite a difficult thing for us to be able to do.

But where possible, we might look at novel protein options. Whether that's a commercial novel protein diet or a home cooked novel protein diet, either of those two things can be fine. I suppose increasingly we tend to use hydrolysed diets because that just tips the balance in our favour a little bit more.

Although it's really important to note that hydrolysed diets on their own are not necessarily enough. We know from some of the human evidence that around about 40% of people will still react to a hydrolysed protein if they're allergic to the parent protein. So where we do use hydrolysed diets, we try and make sure that those hydrolysed diets are also based on a novel protein source and there are a few of those that kind of fit the bill.

Now, where we do home cooked diets, in the short term, we may sometimes use non-balanced home cooked diets, but if we're using those in the long term, or we're looking at diets that have multiple aspects to them, so if we're looking for very, very low fat, novel protein diets, for example, we would tend to. Have those formulated by a nutritionist. There's various nutrition services around in the UK.

We often use Marge Chandler at the Vets Now Hospital in Glasgow, but lots of nutritionists are around the place and they can formulate diets for you, so that you can then make sure that those are balanced and, and they usually then have a supplement that is included within that. Of those hydrolysed diets then, as we said before, we're going to try and use hydrolysed diets that are that are also based on novel protein sources. So we use a lot of Purina HA it's a soya-based diet.

We use a lot of Royal Cannons and allergenic, which is a feather-based diet. I generally try to avoid the use of ZD. It's a chicken-based diet.

Chicken liver is the primary protein source and so it's not novel for most of our patients, but you know, some, some animals can still react positively to to ZD but it may just be a less ideal initial choice. Some of these come in both wet and dry formulations such as Purina HA. Some of them will only come in dry formulations such as anaergenic, and that can make things a little bit more tricky as well.

It is harder in cats, again, when we want a mixture of the two, so we use a reasonable amount of the Decker's diets, the specific sensitivity, type diets. So the one that we use most often is called allergen Management plus in in cats, which is a hydrolysed salmon-based diet, which is probably one of the, you know, the best that we can get from a commercial diet option in cats, but it can be, can be tricky definitely to try and find those options if we want both wet and dry. So I put antibiotic trials in here, as I mentioned before, I'm not at all an advocate of performing antibiotic trials.

I think we need to be very, very cautious, obviously in the, the kind of current situation that we're in with antibiotic resistance that we're seeing to try and be very responsible in the way that we prescribe antibiotics. And I think based on the evidence that we have, antibiotics. Trials are not something that we would routinely advocate.

Where they were used in the past, drugs such as metronidazole, Tylacine are are kind of commonly reported. So I put them on here, I mention them so that you're aware of them. There's some doses there if you are so inclined to use them, but I would really encourage you against doing routine antibiotic trials.

Really where we use antibiotics in gut disease, we should have a clear disease that we are treating. Something that we really think that there is a high probability that it will be responsive to those antibiotics. So for example, histiocytic ulcerative colitis or boxer colitis would be a justified reason for us to use antibiotics.

We know that that is a bacterial disease, but just as a, a routine, therapeutic trial, we try to avoid the use of antibiotics where we can. We're gonna talk a little bit later on about how we can look at some of the other options to manipulate this dysbiosis, this abnormality in the in the gut flora that we see in cats and dogs with chronic gut disease. So if we're in a situation where we've satisfied ourselves, as we were talking about before, that this is likely to be a a chronic entroopathy, and we have perhaps got to the point where we've failed diet trials, we've failed other trials looking at trying to address the, the dysbiosis, so that may be things like probiotics, for example, that we'll talk about in a moment.

We may find that we get to the point where we're considering immunosuppressants, and I suppose most of us before that would advocate then the collection of gastrointestinal biopsies. Now these go in and out of fashion a little bit, because particularly from an inflammatory disease point of view. They do sometimes tell us what we already suspect, i.e.

There is inflammation there. But we do get a bit of information around the structure of the gut, the presence or absence of things like concurrent lymphaectasia, which may have an impact on our dietary choices, looking at fat content, for example. But probably most importantly, it is coming back to the idea that we want to exclude the possibility of a of a lymphoma that we haven't picked up in other ways.

Particularly in cats, these kind of low grade, these small cell lymphomas that I'll mention a little bit later on, those can look really identical. To a chronic inflammatory entropathy, and can behave, you know, for, for long periods of time in a similar way. In dogs, more often when we see, neoplastic gut diseases, they're more aggressive forms of lymphoma, but, but low grade lymphomas are likely to occur from time to time in dogs as well.

So gut biopsies can be useful in that setting of finally ruling out other diseases, but also looking at the structure of the gut, looking at the inflammatory infiltrate. So of course I risk teaching you to suck eggs a little bit by going through the various methods of taking gastrointestinal biopsies, but it's worth just flagging a couple of aspects of this. Of course, gastrointestinal biopsies can be collected in a few different ways, the primary being surgical versus endoscopic.

I guess there are now some variations on surgical, being lab assisted, etc. But broadly. We're gonna talk about endoscopic versus surgical.

I think for me, the method by which you obtain your biopsies is largely irrelevant. I consider these things pretty equivalent in terms of their diagnostic yield. There is obviously gonna be a little bit of a difference in terms of the risk between the two and the recovery time and all of that kind of stuff, but I think I consider them largely equivalent otherwise.

The times that I think that endoscopic biopsies are definitely preferred is of course in patients who are markedly hypoproteonemic in our protein losing enteropathy patients where we might think that the risk of taking surgical biopsies is is then unacceptably high because of that risk of breakdown in that setting. But I think otherwise I would consider them the same. There have over time been suggestions that endoscopic biopsy has a higher chance of being, you know, less representative of the disease process and therefore missing disease.

But I think for me the evidence on which that was based is pretty kind of sketchy really. I think it was based on comparing bad endoscopy to good surgery, which was a pretty unfair fight. So I think we consider them the same, and we'll talk in a moment about how we can make sure we maximise the yield that we get with endoscopic biopsies.

You may see increasingly suggestion of the use of other modalities, so for example, capsule endoscopy, which has become available now to give us visualisation of the, the inside of the gut as these capsules pass through, and they make some suggestion that they can diagnose things like that. I think I would refute that fairly. Strongly, the evidence we have in cats and dogs is that the gross appearance of the gut is not particularly helpful in terms of, of diagnosing disease of the gut, unlike in people.

Therefore, we do really need to collect those biopsies when we, when we're doing endoscopy or, you know, any other method, and I think looking at the gut on its own is really not that helpful. Where we do take biopsies, how can we make sure that we absolutely maximise the amount of information that is obtained? Well, we should examine and biopsy as much of the gastrointestinal tract as possible.

There is plenty of evidence that suggests that in many cases, the diseases will be most severe in the distal part of the small intestine, i.e. In the ilium.

And so where we are doing endoscopic biopsy, we should where possible, via the lower GI approach, access the ilium and take ileal biopsies, as well as gastric, duodenal and colonic biopsies. So we take as much of the of the gut as we can. And we should make sure we take multiple biopsies from each site, so ideally at least 6 to 8 biopsies from each of those areas.

We need to make sure we have good biopsy technique that we get our forceps nice and well buried within the mucosa to get good chunks. We should make sure we've got biopsy forceps that are appropriate, so we generally use disposable biopsy forceps. I generally use spiked biopsy forceps.

We make sure if we do use disposables that we're replacing them regularly, we're not reusing them 20 times, and that we use biopsy forceps that are as large as possible for the size of the working channel of our endoscope, so we can get nice big chunks. When we then submit these, we should make sure we use a pathologist that is comfortable with looking at endoscopic biopsies and where appropriate, we might use other staining methods. So when we talk about those two things, we should have pathologists that use the WSAVA standardised schemes for looking at histopathology from the gut wall.

And that will tell us about the predominant cell type, but also we'll look at these structural changes that can be interesting to us. The additional staining techniques, well, the one that's probably most often used now is going to be things like PCR, so there's PCR for antigen receptor rearrangements, PA, that's a way for us to look at the clonality of the lymphocytes within that tissue, so we can differentiate polyclone. Lymphocyte proliferation, such as we would see with inflammation, from monoclonal lymphocyte proliferation, such as we would see with neoplasia.

So PA is quite a useful technique and and has been demonstrated to be quite helpful, where we're differentiating some of these lower grade forms of lymphoma from an inflammatory disease. Other things, so fish, if you haven't come across fish before, that's a way of staining fixed tissue for bacteria can be useful to diagnose things like that, ulcerative colitis that we were talking about just now, where we want to look for bacteria within the tissue. And sometimes things like immunohistochemistry, particularly when we're wanting to to type neoplasia.

So what is our expectation in dogs who have chronic enteropathy? How do we kind of expect them to respond to these different things? Well, the data suggests that in our kind of lower grade disease, as we were talking about earlier on, that around about 75% are likely to be diet responsive, but that.

Maybe even higher than that in younger patients. If you're below 18 months to 2 years of age, it could be as high as 90% of dogs that will respond to diet. So it's worth us in young dogs playing around with diet for a bit, sometimes trying more than one diet to see what the response might be.

You don't need diet trials to be overly prolonged in dogs and cats with gut disease. Again, the evidence suggests that we get a response in most cases within kind of 2 or 3 weeks. So unlike with perhaps skin disease, where we're talking about 8 or 12 week diet trials, from a gut point of view, 234 weeks is probably enough.

The historic data suggested that some dogs would be responsive to antibiotics, as we've spoken about, we're no longer gonna do those trials. And then actually in those low grade dogs, it may only be about 10% that ultimately end up needing things like immunosuppressants. That is slightly different in those more severely affected dogs such as the protein losing entropathy dogs, where they have a lower probability of responding to diet, a much higher chance that they might need immunosuppression, and a reasonable chance that they will end up dead within a relatively short period of time of, of presenting.

And that death or euthanasia in dogs with protein losing enteropathy can be due to initially poor response to treatment and and death through the consequences of that. Or unfortunately, it can also be a little bit further down the down the road. Dogs who are ultimate.

The euthanas because they require a lot of drugs that has then an impact on their quality of life. So protein losing andropathy is a severe disease. You know, severe gut disease is an unpleasant thing to have and it does have a high mortality rate associated with it.

So let's look a bit more then at some of the other treatments that we may use in those dogs and cats where diet alone has not been effective. Now historically, we always thought that that more severely affected dogs, such as those protein losing entropathy patients would always require drugs, although there is a little bit of evidence to say that diet alone may be possible. The problem is it's a relatively bold thing I think to do to try and pursue diet trials in animals that have very low protein levels, but you know, there is, there is some evidence to say that that may be a justified approach.

More often than of course, we're going to be looking at steroids as our kind of first line immunosuppressant in animals with inflammatory chronic enteropathy who have failed to respond to those other therapeutic trials. And and prednisolone is gonna be the most common thing that we might use. The kind of doses that I would tend to start dogs with gut disease on vary a little bit based on the size of the dog.

So we do need to use immunosuppressive doses, we do need to be up at that kind of 1 to 2 milligramme per kilo type dose. But we also need to be aware that the adverse effects of steroids, these kind of caketic side effects of steroids can be quite marked in some of these dogs. And of course these can be dogs who also have some of those signs already, you know, if you've had.

Chronic gut disease, you may already have pretty poor muscle mass. If we throw some steroids on top of that, actually, we can make you pretty skeletal. So we also need to, to weigh those things up and sometimes be more conservative with our steroid dosing than we might be otherwise.

So, I would probably sit closer to the kind of Mg per kilo per day dose in, in most patients, but sometimes we push it a little bit more. And of course, be aware of all of the kind of usual pesky side effects that we're gonna see when we, when we use steroids. Now of course for that reason, there is interest in alternatives to the use of prednisolone.

And sometimes that is drugs we use alongside prednisolone to try and allow reduction in steroid dosing, sometimes it is alternative preparations. You may or may not be familiar with budesonide. It's an enteric coated form of steroid, it has a high first pass deactivation.

So the idea behind budesonide is that it has high local activity within the gut and a marked reduction in the systemic absorption of that steroid. Works reasonably well in people for that reason, but unfortunately, the results in dogs are a little bit disappointing. So the, the literature that compares this suggests that budesonide has no real benefit over prednisolone from an efficacy point of view and seems to result in similar adverse effects.

So occasionally we will try budesonide in dogs who are very dependent on high steroid doses but have significant adverse effects. But if, you know, we're hoping that this will be the, the thing that fixes all of those problems, it's not always significantly better. What other drugs then can we consider?

Well, cyclosporin, you know, we're pretty used to using cyclosporin in other immune-mediated diseases. Again, we've got some good evidence in the use of cyclosporin in in dogs who are refractory to the use of steroids, so in a group of German shepherds, and we've got good experience with the use of cyclosporin over time. There is also some thought.

That cyclosporin may concentrate within the gut wall, so we may be able to get away with lower doses than we have to use for some of our other immune mediated conditions. So I think cyclosporin can be a a good treatment to use in some situations. It is pretty expensive, so if you're a larger dog, you know, use of cyclosporin long term can be quite pricey, but a good one to to try.

Another good option would be chlorabil, we use this quite extensively in dogs and cats with, I mean, lots of diseases, but particularly with with gastroenteropathies. And there's some nice work from, from a few years ago from Liverpool looking at comparing in those PLE cases a comparison. Of chlorabil prednisolone to azathioprine prednisolone, and the survival times in the chlorambil group were way way longer than in the azathioprine group.

So it's largely replaced the use of azathioprine on that basis for treating chronic gut diseases. The downside has also become quite an expensive drug to use, so for, you know, medium sized and larger dogs, it can be cost prohibitive sometimes. But in dogs and cats who tolerate cloamucil well, it can be a really nice drug to be using long term, and has, you know, relatively few side effects as long as we monitor these things well.

So we tend to monitor a haematology periodically to make sure we don't see any sign of myelosuppression. Azathioprine, you know, largely fallen out of favour based on that Liverpool work and I suppose based on the availability now of other drugs. So I think we use very little Azerthioprine in general now with immune-mediated conditions.

We touch on it from time to time in some situations. Usually around price point. So azathioprine is one of the cheaper immunosuppressive agents, but that risk, you know, can be a false economy, I suppose, based on the fact we have to monitor azathioprine more frequently and if we do see toxicities, those can become more expensive things to, to treat again.

So, you know, cost can be a benefit of azathyprim, but we have to be a little bit cautious with that. I suppose alongside afiprim we should mention mycophenolate. They have a broadly similar mechanism of action, although mycophenolate has a vastly improved significant adverse effect profile in terms of the, you know, hepatotoxicities and the bone marrow suppression that we see with azathioprine.

The limiting steps we can sometimes see with mycophenolate, it can cause gastrointestinal side effects, which of course makes it a challenging thing sometimes to consider in gut diseases. So we use that a lot now in things like immune-mediated polyarthritis, thrombocytopeniaas, things like that. And occasionally we will reach for it in gut diseases, but personally, it's not my, my first line, you know, additional agent to look at in the gut because of those significant risks of of gastrointestinal side effects.

So to summarise where we might be with our kind of conventional therapeutic approaches, we're gonna be looking then firstly at diet and secondly at at immunosuppressants and then thinking whether there are additional adjunctive therapies that we may need to use alongside that. So if we have patients who. Are nauseous, for example, you know, do we need to consider the use of antiemetics?

Do we need to be looking at gastroprotectants? You know, these are all things that we should think to ourselves as, as part of our, investigation and and management strategies for these patients. So let's talk about some of the newer thoughts when it comes to chronic enteropathy, some of the other aspects that we may be able to target to give us new approaches to managing chronic enteropathy.

Because what you're gonna say to me, it's all well and good, what you've just spent the last half an hour telling us about. But this is all the kind of stuff that we've been hearing about for years. Things haven't really changed.

We've been using steroids, we've been using diets, all right, you know, minor aspects of that changes over time, but, you know, we're largely where we were 1015, 20 years ago from the point of view of the gut. So what's the more recent thinking? Well, I think most of our more recent interest in gastrointestinal diseases is revolving around the microbiome.

So this collection of bacteria and fungi and viruses that live within the gut. And there is evidence in both cats and dogs to say that we get dysbiosis, we get derangements in that normal microbiome when we are looking at animals that have both acute and chronic gastroenteropathies. So a nice example of that, these are heat maps, these are studies that have both.

Actually come out of of Texas, out of the GI lab, looking at the distribution of the different groups of bacteria in animals with and without gut disease. So these are heat maps that show those as different heats, so red to blue, depending on how many of those groups of bugs we may be seeing. So you can see if I bring up the laser pointer here.

So on the left here, this is looking at acute gastroenteropathies, and you can see the left hand section of this is the healthy dogs. And you can see in healthy dogs that they get this big cluster, most of their bugs are, you know, clustered at the lower half of this graph. On the right here, we're seeing then dogs with non-hemorrhagic or acute hemorrhagic diarrheas, and you can see a shift, you can see a reduction in some groups of bacteria.

You can see up here an increase in the fusobacteria ACA. Over the right here, similar graph. This is in our chronic gut disease patients, it's the opposite way around, so the controls are on the right here, on the left here, the IBD dogs, the dogs with entropathy, and again, you can see it at the the bottom of the heat map.

Here an increase, increase in this kind of block of red that tells us that there are groups of bacteria that are gonna increase. So we've shown that there is a shift in the, the types of bacteria that we see within the gut in both acute and chronic gastroenteropathies. Now of course what we don't know is how much of that is caused, how much of that might be affect, you know, is this due to the fact that there is a diseased gut, or is this part of the mechanism of why these animals get chronic gut disease?

And there's lots of work going on to try and unpick the the kind of relative components of that. As there is to look at these derangements in the microbiome and the impact that that has on lots of different groups of disease. So the, the evidence around this now is quite bewildering around not just gut diseases but kidney diseases, you know, neuropsychiatric type diseases, cancers response to chemotherapy, for example.

It's a, it's a whole world that's just being unpacked at the moment. But what that does suggest to us is that if we see animals who have dysbiosis, which we can broadly assume is likely to be the case in most of our patients, should we be trying to do something to address that dysbiosis to try and push those bugs back to a, you know, a more normal flora as part of our treatment. This is very much an area that we're just scratching the surface of.

We have clinical trials looking at this at the moment, but it may be something that's used to, you know, a a useful clinical tool in terms of trying to address these things. How can we do that? Various different routes, so we'll talk about these in turn.

The use of diets, potentially the use of probiotics and the use of faecal transplantation. So, starting with diet, we've known for years and years that diet has an impact on the gut flora and the work has gone on over time and the techniques have improved to kind of demonstrate that. And a lot of that is around the types of fibre and the amount of fibre within diet.

We all know that fibre is good for our gut. So we're now starting to see diet. That have certain blends of fibre in them that may benefit some of the particular groups of bacteria within our gut.

And I think trying to understand the benefit that they have and and the role that they may be able to play in some of these gut diseases is very useful, but there may be diets that can exert a positive effect from a gut flora point of view. So what about faecal transplantation? Pretty simple idea, you know, we take faecal matter from a healthy donor, you know, a donor without gut disease, and we put that stool into our recipient, our dog or cat with gut disease to see if we can improve the kind of composition of the the gut flora and see if that might infer a health benefit.

It's a pretty simple thing for us to do. So we take some donated stool. This should be taken from a dog who's not had recent antibiotics, that is, you know, not, not overly young or old, he's healthy, he's fed a standard commercial diet, you know, he's not on a raw diet, for example.

We take that stool, we. Put it in with some saline. We liquidise that in the blender.

We sieve it to remove the larger particles from that so that we've just got that, that soup. And then we administer it to our patients. And at the moment we tend to administer administer faecal transplantation by a retention enema.

So we take a volume of that material. We do an enema while the dog is sedated so that they're a little bit sleepy, and we try and keep it in then for at least 20 minutes or so. We usually use a large foley catheter, something like that to try and get it as far as possible into the colon.

You can administer it in other ways, and, and the evidence in people suggests that it actually doesn't make too much of a difference whether you give it, you know, by endoscopy into the duodenum, for example, or whether you're giving it by retention enema. But of course retention enema is more straightforward in terms of the administration that we have. Now, as I said before, there's lots of interest in faecal transplantation going on.

We have a clinical trial that we're involved with looking at the use of faecal transplantation early on in disease alongside, standard therapy such as diet change, and we're interested to see whether that gives a benefit in terms of improving the response to more conventional therapy compared to to other approaches. Equally many people are using this later on in the disease if the response to other more conventional treatments is poor. So I think we have to watch this space a little bit to know when we ought to be using this intervention, but it can certainly have some benefits in terms of exerting a pressure on the gut flora.

There's some human evidence around this, so there's lots of clinical trials again in the human world, looking at the, the, the use of faecal transplantation as a treatment. You may have heard of its use for the treatment of C. Difficile, which is very difficult to treat enteric infection, often picked up in people who are in hospital and have had lots of antibiotics.

It's quite a tricky disease to treat, but the response rate to faecal transplantation is really excellent, well over 95. So it's becoming something of a standard of care for C. Diff in people.

But of course, for that reason, they're also interested in other groups of disease. And so some of the diseases that are broadly similar to the diseases that we're going to be treating, so Crohn's disease, ulcerative colitis, there's been some work looking at those. And around about 25-30% of people with those kind of conditions can show some improvement.

What we should though be aware of is that in some of those studies, some people get worse after faecal transplantation and so we need to understand a bit more about, you know, which people may improve and which may not. The other thing that's become a challenge in people, and I think this is less of a concern in our world, is that there has been in the states, in a person who is involved in a clinical trial looking at faecal transplantation, a single death of a person who had a faecal transplant, picked up an enteric infection and ended up succumbing to that. Now that for a while halted many of the clinical trials because they were worried about that risk for harm, but actually if you look at that in more detail.

The person in question was heavily immunosuppressed and it was actually a failure of their screening processes. They should have screened their stool for that disease, and it was missed in their screening. They picked it up when they re-screened the donation.

So they've looked a lot more at how they screen these things rather than anything else. And as I said before, we don't really worry so much about enteric infections in our patients, so probably not something we have to be too concerned about. What about evidence in our patients?

Well, you know, there's various publications then that have appeared over time. There's a couple of case reports early on showing some response in dogs to faecal transplantation. You may have seen this more recently looking at the use of FMT in puppies with parvovirus, where they had a faster resolution of their diarrhoea and a shorter hospital hospitalisation period in dogs that were given FMT as part of the treatment in parvovirus, which I think is really, really interesting.

And then Silka at Edinburgh looked at a an observational study, so she had a questionnaire looking at practitioners' experiences with faecal transplantation. And she found that around about 50% of cases showed some response to faecal transplantation, but there were some adverse effects reported, such as increased severity of diarrhoea. So yes, we're showing some positive that it may be a useful thing for us to do, but again, we may also be in a situation where there's a chance that we can make some things worse with with FMT.

And this just shows, this is again some work from the GI lab looking at the dysbiosis index, which is one of the markers that they use to look at evidence of dysbiosis, to show that if you take dogs who have dysbiosis, which you can see on their graph are the dogs that are in the positive on their dysbiosis index. If you give them a faecal transplantation, you do resolve that dysbiosis, you put them into the negative, which is normal for their assay. And then in some patients they seem to stay normal, such as the, the lower curve you can see there.

In some patients they seem to improve for a bit and then they develop a dysbiosis again. Again, we need to understand a lot more about, you know, which dogs do well and which dogs do not do so well, so that we can, you know, explore these things in more detail. So what can we say about faecal transplantation at the moment?

Well, I think we have to say there is some promise, with the early experience of this, but we need a lot more work to know whether we should be routinely using this and in which patients we should be routinely using it if we think that that's the case. So what about probiotics? Again, probiotics are an enormous topic and we could talk probably for an entire lecture about which probiotics and when we ought to be thinking about using probiotics.

What I would say is that at the moment we have very little evidence to suggest that probiotics are a useful thing for us to use in chronic gut disease. The one publication that has shown some promise is this one here, . Which is an oldish publication now looking at a combination probiotic, this thing called VSL Number 3, which if you're interested in using it, it's no longer called VSL Number 3, in the UK it's now called Vivo Mix.

But this was using a multi-strain, high potency probiotic and comparing that to dogs who were treated with prednisolone and metronidazole as an alternative. Now the interesting thing in this publication, ultimately the two groups did the same, so the response rate was the same to the probiotic compared to the, the standard therapy, the predometronidazole. The downside of the probiotic, it was slower to show that positive effect.

But you know, I think this is an encouraging thing that perhaps there are a subset of dogs that may respond to probiotics. The thing to flag about this probiotic, as I said before, it's a multi-strain probiotic that makes it quite different to the probiotics that are widely being offered into the veterinary market, which tend to be relatively low potency and typically single strain probiotics. So for me, if we are going to use probiotic trials in dogs with chronic.

Or cats with chronic enteropathy, and I think that's a justified thing for us to do in our knowledge of dysbiosis. We probably should think carefully about the kind of probiotics that we might use and maybe these high potency multi strain probiotics are a more logical choice if we're, you know, thinking about that as an intervention. Overall, what can we say about the prognosis in dogs with chronic enteropathy?

Well, it can be very variable, as we've touched on before, it is broadly dependent on the disease severity. Animals with a protein losing enteropathy can have a very guarded prognosis over time. But really the best indicator is going to be the.

Response to treatment. That doesn't necessarily correlate with things like histologic improvement, doesn't always correlate even with things like biochemical improvement, but the clinical response to treatment is the biggest indicator of how you, how you're gonna do long term. You can look at other scoring systems, you know, monitoring things like C-reactive protein, but if we introduce a a treatment and that improves your clinical signs, that's gonna be the best marker of how you're gonna get on.

So, before we finish, a couple of words about cats and their variations that we should be aware of. We do of course see chronic inflammatory enteropathy in cats in a very similar way to dogs, and our approach to those things is going to be very similar. You know, we're going to work them up in the same way, we're gonna do the same tests, we're gonna look at therapeutic trials, diets, etc.

But when we see inflammatory gut disease in cats, it's very common for that to be part of this triad of inflammatory diseases that that we see within the abdominal cavity, this triad that we likely then refer to as triaditis. That is inflammatory gut disease, inflammatory pancreatic disease, and inflammatory liver disease. And actually if we look for this in cats that present to us with us having a suspicion of a chronic entroopathy, it's really common that we're going to see these things.

Equally, if we see a cat that presents to us with an inflammatory or an infectious liver disease, cholangiopatitis for example, it's very common that we will find evidence to support the idea that there's also an inflammatory gut or an inflammatory pancreatic disease. We don't completely understand the link between these things, it may represent a translocation of bacteria between these areas, but it's still an area of interest for many people. But when we do approach these, we should just bear in mind that these things may be present, and our approach to managing them may need to be broader.

That means that if we are looking at biopsies, for example, still a reasonable proportion of our cats when they're having biopsy may have those performed surgically so that we can take liver biopsies at the same time if we're interested. So just be aware of those and consider them at the point that we're, we're seeing these patients. In the first instance, diet trial still is, is likely to be our first approach alongside treating bacterial complications.

So if we do find a bacterial cholangia hepatitis. The other condition, I mentioned it before, but it's worth being aware of, this low grade lymphoma, feline small cell lymphoma, mostly reported in cats, but occasionally reported in dogs. This is a low grade, indolent form of lymphoma that looks very similar to the inflammatory entropathy that we see in dogs.

The reason that it's important to differentiate is because we know if we can pick up on this and we can therefore get our treatment in place appropriately and we tend to use a combination of prednisolone and chlorambil, the survival times can be really good. So we should just again have that in mind when we're investigating these patients. So that's been a bit of a whistle stop tour through chronic entroopathy.

I hope it's been useful and as I said before, if you do have any questions, my email is at the front of this, do get in touch. Happy to discuss any of those aspects at any time. Hope it's been useful to you.

As I mentioned at the start, I'm involved in a new referral hospital, it's called Blaze. We open later this year in November. If you are in the Midlands or indeed further afield and you're interested in what we're doing, do check out our website and you know, do get in touch when we're open if we can help you with cases.

Many thanks