Hello, everyone, and welcome to this 6th webinar. We're gonna discuss about inflammatory bowel disease and some other selected intestinal diseases. So I suspect you see patients with gastrointestinal signs extremely frequently, and a number of those will probably turn out to have inflammatory bowel disease, which we know is this sort of encompass all term.

That includes patients that have inflammation in their guts, secondary to food allergy, secondary to parasites, but often secondary to unknown causes, and it's that latter group that we then use things like corticosteroids and other drugs to try and dampen down inflammation. So this is a a case example to introduce some of the concepts. So this was Josie, who was a 615 year old female neutered Weimarana.

She came to see her, she got a a month-long history of progressive diarrhoea. It was, it was worsening in in frequency and severity. There was a slight increase in frequency.

There was more faeces passed each time she defecated. There was no dyschesia, no blood or mucus, so you should already be thinking to yourselves, you know, has she got small intestinal or has she got large intestinal disease, because the differentials differ and the approach to the case can also differ. But the caveat is that many of, feline and canine patients have got both small and large intestinal disease.

She's also intermittently vomiting, there'd been some weight loss and her appetite was variable, she was just a bit picky. Clinical examinations, she had a slightly reduced body condition score. We felt that we could feel some abdominal fluid fluids.

There was, yeah, soft faeces on the thermometer, there was no blood, no mucus in those faeces, and there were no other abnormalities on, clinical examination. And then she'd previously been managed with a hydrolyzed diet, and she'd been fed that exclusively for about 3 to 4 weeks, but there'd been very little change in her clinical signs, and then she was routinely administered various antthalmitics. So yeah, these are some of the differentials.

So, we decided that it's most likely that she had small intestinal disease, particularly with a weight loss that tends to fit more exclusively with small intestinal rather than large intestinal disease. But you'll remember, of course, that in large intestinal disease, animals tend to defecate more frequently and there is sometimes blood, fresh blood and mucus in there, so she wasn't showing any of those things, but particularly with the weight loss, small intestinal disease was felt to be most likely, and so these are differentials of small intestinal diarrhoea. And, you know, we start with some small intestinal diseases, inflammation.

This thing called antibiotic responsive diarrhoea or small intestinal bacterial overgrowth or other names that we'll just briefly touch on. It's probably not really a sort of a common condition now, or at least it's not the case that we should be treating patients with diarrhoea with antibiotics, as you'll be aware. Tumour, either, you know, diffuse tumour or more focal tumour, partial obstruction, lymphaectasia, crip disease will touch on, and a couple of other less common intestinal causes.

But of course, we can also see, Intestinal, we can also see small intestinal diarrhoea to sort of extraintestinal causes, so liver disease, which is usually secondary to portal hypertension. That's the reason why they develop diarrhoea, renal disease, in dogs, hypoadrenal autism, various drugs and toxins, chronic pancreatitis. Exocrine pancreatic insufficiency is an important one.

Obviously, we typically see it in young German Shepherd dogs, but occasionally other breeds can develop it, and they can be middle-aged or older, usually a result of chronic pancreatic inflammation. And infectious causes, there's not really that many infectious causes of chronic diarrhoea, although, you know, it's common that people perform faecal analysis to look for bacteria, but there's very little infectious causes really in both dogs and dogs and cats. But we need to be thinking about, endoparasites, and things like Eyardia is important, tricuris.

Salmonella, Campylobacter possibly as well. I mean, Campylobacter probably doesn't cause disease in dogs or cats. It's just we worry about it for a, for a zoonotic potential.

And salmonellosis is not really very common in dogs or cats. You might see it a bit more in cats, particularly cats that hunt, but often it's causes hemorrhagic diarrhoea and patients are vomiting and they're unwell. And then the other important, really important group is the dietary group.

So, you know, intermittent scavenging, dietary allergy, possibly dietary intolerance, although most of the time we tend to see Patients with dietary intolerance that present at an earlier, early age, but not, not always, but I guess true dietary intolerance is not that common. So a whole load of differentials for this major problem which is small intestinal diarrhoea. So, you know, what, if this was your case, what would you do, next, you know, would you think about changing and trying another, novel protein or, hypoallergenic diet for sort of 4 weeks?

Would you do serum biochemistry, maybe do some imaging by way of radiography or CT? You know, the, the, none of them are, none of them are really wrong. We definitely see dogs that have gastrointestinal disease that quite significant gastrointestinal disease that we feel have got a dietary allergy because it's quite common, and we change the diet and it doesn't improve, but then we try a second hydrolyzed novel protein, hypoallergenic.

Diet, one of those and you get a significant response. So sometimes you've just not selected the most appropriate diet, so it's not wrong to use another diet, but you know, I know that's sort of been through diets and lots of tests already, may not be happy with you just suggesting an additional diet. And also because Josie's got quite severe disease and, you know, the suspicion is that she has got ascites and so that could be a, you know, a quite a significant factor in how quickly we should try and manage her, serum biochemistry is obviously a sensible thing to try and look for those sort of, You know, extraintestinal causes of diarrhoea, you know, pancreatic disease and liver disease, and renal disease and others, and also look for the consequences of diarrhoea by way of electrolyte abnormalities or azotemia.

Abdominal radiographs are of sensible, you know, imaging. To do as well, because we're gonna look for, you know, foreign bodies, intersection, gross le lesions, sizes of organs, etc. Etc.

But ultrasonography is generally the sort of preferred imaging. Most patients with diarrhoea at least. Abdominal radiography is good, very sensible first line for vomiting patients.

And then, yeah, we could do abdominal CT but maybe we're not gonna jump to that yet before we've at least done some biochemistry and look at, general health. So yeah, we, did some clinical pathology to look for extraintestinal causes and these are the results. Maybe you want to just stop the webinar and just work through those results yourself to try and determine what's, what's going on.

And you can see that there is a mild increase in glucose, but that's just a stress response. But the most critical things are that the total protein is reduced and that's both a reduction in albumin and also a reduction in globulin. And there's also a mild to moderate increase in liver enzymes, increase in ALT marker of apatocellular damage, increase in biostasis, which is indicated by an increase in ALP.

So yeah, the critical thing here is significantly low albumin, so you'll already be thinking, well, you know, Josie seems to have got CITs on on examination. Could that be due to the significantly low albumin and loss of oncotic oncotic pressure. And that's sort of, you know, there's a number of causes of a low album and as you'll remember, it can either be due to, decreased production, so animals with liver failure, or it can be due to increased loss.

So either loss from the kidneys or loss from the gastrointestinal tract. And if you have a patient that's got both low albumin and low globulin, that tends to point towards protein losing enteropathy, because the damage is so significant that you can lose big molecules like globulin, whereas you shouldn't get low globulin in patients with protein losing nephropathy. So, you know, finding a patient with That has diarrhoea, that's got a protein losing enteropathy, should start to ring alarm bells and you should really be thinking about quite significant gut diseases.

So, you know, marked inflammatory bowel disease, sometimes that's eosinophilic, sometimes it's, you know, lymphocytic plasmacytic lymphaectasia. Touch on that condition in a, in a moment and neoplasia and it's usually diffuse neoplasia, i.e.

Lymphoma. And so, of course, the next sensible step, would be to do some abdominal imaging, by way in, in, her case by doing, ultrasonography. And there's some reference intervals there, not expect you to, to remember those by any means, but, there was generalised intestinal wall thickening.

And no loss of layering. There was some free abdominal abdominal fluid, and there was some mild mesenteric lymphadenopathy. So we decided to stick needles in the mesenteric lymph nodes.

That's what we saw. You can see is a, a mixed population here. So there's some red blood cells and a background protinaceous material, but then a whole mix of, predominantly predominantly small lymphocytes, but also some plasma cells.

So, there's a plasma cell on the very right there. There's another one towards the, towards the centre. There's sort of a group of three plasma cells up at the sort of, 1011 o'clock region, and many of the other cells are small lymphocytes.

There's very occasional neutrophil across to the right-hand side of the image. There's 3 or 4 neutrophils there. So this is a sort of very mixed, mixed population suggestive of a, a reactive lymph node.

And then we moved on, so, you know, we sort of ruled out as best we can. Extraintestinal diseases, there's still some things on there. But, you know, we want to ideally try and get some, some samples of the samples of the gastrointestinal tract, and there's different ways of doing that, and the game will touch on those in a moment, but in Joe's.

It was decided that she should have endoscopic biopsies, and there was nothing that was visibly grossly abnormal, but of course you should always still take biopsies and several biopsies were taken from the stomach and also from various parts of the small intestine. And the histopathology indicated there was a mark to moderate infiltration by plasma cells and lymphocytes with a few earsinophils, and the conclusion was that she'd got moderate to marked inflammatory bowel disease. The issue is, of course, with endoscopic biopsies you get very small pieces of tissue.

But of course it's got the advantage that it's minimally invasive. Versus exploratory laparotomy, which is a great way to collect biopsies, because you can get full thickness biopsies of multiple different places, some of which you might not be able to reach with the endoscope. But of course it does involve a celiotomy and the issues around wound healing potentially in a patient with low blood albumin.

So let's have a look at inflammatory bowel disease. It's this sort of, and then the, the, the terminology is changing. You may start to come across new terminology for chronic inflammatory enteropathy, CIE is sort of taking over from, from IBD just to confuse everyone once we've got used to one particular term.

Anyway, IBD is the collective term for a group of chronic. Interopathy. Characterised by, persistent or recurrent gastrointestinal signs and inflammation of the guts.

So, you know, by definition IBD is a disease of inflammation and the difficulty. Is that there's a number of things that can cause gastrointestinal tract inflammation, so it's trying to identify which, which one of those it is. And so, you know, the aetiology of inflammatory bowel disease is multifactorial and, you know, it's still not fully understood in humans and it's definitely not understood in in dogs, but there's You know, definitely a, a component of the host's immune system or inadequate host immune system.

We, you know, see increased incidence of IBD in certain breeds, as I'll show you in the next, next slide. You know, there's definitely environmental factors, some of which might be dietary related. But they're very, you know, important, component of why patients develop inflammatory bowel disease is due to changes in their gastrointestinal tract, flora or microflora.

So yeah, IBD is, is seen in dogs and cats, and there's certain breeds have got an increased risk of them developing, IBD and, some of the more important ones are listed on, listed on there, we also see in, in Siamese cats. And there's various things which can trigger gut inflammation as already alluded to. It might be a, a food, a dietary allergy, so we call those sort of food responsive inflammatory bowel disease.

It might be animals that have got abnormal bacteria or overgrowth of certain types of bacteria or, you know, dysbiosis, different, you know, and, . Different types of bacteria within there, gastrointestinal tract, and so we sort of call those guys antibiotic responsive, IBD, and then patients that don't fall into those two categories that, Often, but not always respond to immunosuppressive drugs or anti-inflammatory drugs are the ones we call idiopathic. So, you know, again, IBD just saying inflammation in the gastrointestinal tract leading to chronic GI signs.

The difficulty is identifying, identifying the cause. And there's one or two sort of specific forms of inflammatory bowel disease that occasionally you'll come across in specific breeds. So there's a, a particular form of inflammatory bowel disease in Bazenges, not that we see very many, many bazenges, but they can be very severely affected, affected, sorry, and they can actually have a high globulin, which is just because of a, a massive inflammatory response.

And then soft coats and wheat and terriers, develop, protein losing enteropathy or IVD associated with protein losing enteropathy, and about half of them also have protein losing, nephropathy. And then you, well, I'm sure have heard of this condition which is called granulomatous colitis. It's known by other terms, previously, histiocytic ulcerative colitis.

It seemed pretty well exclusively in boxers and also in, in, in French bulldogs, although we occasionally think we diagnose it in other breeds. And it was originally thought to be an idiopathic form of quite severe inflammatory bowel disease, and I remember seeing more than one boxer dog in practise with really severe GI signs. These dogs can have really marked.

Colitiss-like signs, you know, frequent passage of faeces, straining lots, blood, mucus. The unusual thing though is that it's a predominantly large intestinal disease, but they also lose, can lose significant, significant weight. And there's various, various, publications on this condition.

It was probably first identified about sort of 1520 years ago now. We still see cases probably less, less, much less commonly, I think, than we used to, but look out for it. And it's, it's thought to be associated with invasive intramucosal E.

Coli, but also dogs with. This condition have been shown to have a in part decreased local immune response, so they've got decreased neutrophil function and other things. The good thing is that it responds very well to fluoroquinolones, although the bad thing is that there is increased resistance to, particularly to enrefloxacin.

So we used to give these dogs lots of immunosuppression, they used to not improve, stroke get worse, so we used to give them more, and then they used to get used to be euthanased, whereas now they respond with normally a 6 or 8 week course of a floraquinolone. If you, your first line is then refloxacin, and the dog doesn't respond very well. That you'll need to change it to something like Marbafloxacin.

So look out for this condition in boxers predominantly, but also French bulldogs, maybe, maybe occasional other breeds as well. So, as I say, yeah, there is, there is some quite significant resistance seems to be. Identified to, to fluroquinolones, particularly to enrofloxacin, but I suspect now there'll be resistance to marbafloxacin, so you may need to change the drugs further.

What about lymphangectasia, we've alluded to it earlier as a cause of protein losing enteropathy, generally quite a bad gastrointestinal tract, and these, these two images here are just, showing biopsy samples, top one is a lower power, bottom one is a high power, and that great big, you know, white space there is dilated lacteals. So in this condition, you have dilation of the lymphatic vessels and lymph leaks out into the intestinal lobe and of course gets lost in the faeces, so you're losing lots of protein and triglycerides and lymphocytes and fat so or vitamins, amongst other, other things. So you can see if there's a massive loss of protein while these animals develop low body proteins.

And it can be primary. Not, not that common. It's, it's congenital, but it can be primary idiopathic, i.e.

No underlying cause, or secondary to another, another condition. And it's probably secondary in most cases. It's just that we don't truly identify what the underlying cause is, but some sort of inflammation in the gastrointestinal tract that's blocking the lymphatic.

So, you know, it often seems to be associated with inflammatory bowel disease. So, you know, we, as you'll see in the moment, we often sort of immuneo suppress, press these dogs as well. It's can be challenging to diagnose.

I mean, it's easy on something like this with full fitness intestinal biopsies, but on pinch biopsies, gut biopsies taken via an endoscope. It can be a bit more challenging to, to diagnose it. One other thing that you, you might see on ultrasonography is that you can see, sort of bright white specks within the gastrointestinal tract, and that's just that tends to be the lactes that are full of, fatty, fatty fluids, so that's why it's showing up, brighter white on the, the mucosal sides, oh sorry, the submucosal sides.

So, you know, you can try and, try and diagnose it from imaging maybe, but ultimately it's a sort of histological diagnosis, . And as I say, primary disease occasionally, but most of the time it's secondary probably to, you know, inflammation within the gastrointestinal tract that's blocking lymphatics, but it could be nearoplastic infiltration or possibly other, other causes. And these breeds of dogs have been reported to have a high higher incidence of lymphaectasia.

But again, you can see it in any, any breed of dog, and it's also seen occasionally in, in cats. The treatment for it, in case we forget to touch on it later on, is, you know, treating any underlying condition, which is probably usually inflammatory bowel disease, but then also a low, low fat diet can sometimes help these dogs as well. This is another thing, it's been around for, you know, a couple of decades now.

It's, it's infrequently reported, but occasionally we see histopathology reports that refer to this condition. It's called cri crip disease. And there's just an abstract there of one of the sort of the first case reports by Mike Willard and others.

So the hallmark of this disease is really severe and you obviously see this histological diagnosis. You obviously find severe dilation of the intestinal cryps that are filled with mucus and epithelial cells, plus or minus inflammatory cells. And it's sometimes but not always found in combination with inflammatory bowel disease or lymphangectasia.

This is probably one where you would be better taking endoscopic biopsies, because you're obviously gonna get that mucosal service where the, where the rips are. And it seems to be more prevalent in Yorkshire terriers and also, Rottweilers. And it is associated with protein losing enteropathy.

These animals lose large amounts of their protein protein into the lumen of the gastrointestinal tract, which gets lost in faeces. We don't know the cause of it and we don't have a specific treatment apart from, again, treating the underlying disease, be it inflammatory bowel disease or lymphangectasia. OK, so, we sort of went through, went through Josie, and, I'll just sort of give you a little bit more detail about how we diagnose animals with IBD or chronic inflammatory enteropathy.

So just some sort of take home messages. So, you know, as we saw with Josie doing serum biochemistry, haematology are a sensible first line step to look for extraintestinal causes of diarrhoea. But also to look for sort of concurrent conditions, concurrent diseases or consequences of the, chronic GI signs.

So be it as Josie did, have low albumin, but it could be other things like low cobalamine. Parasite screening is, you know, it's probably OK to do. It's, but I would probably be selective rather than just send faeces off for multiple tests.

We had a case today that had a sort of a faecal PCR panel for multiple pathogens, some of which I've never even heard of. So they can cost quite a lot of money and as I say, there's very few infectious causes of diarrhoea, you know, obvious exclusion, obvious except. Obvious exceptions would be things like parvovirus, so of course critical that we find out about vaccination history.

But there's not that many, many others, we talked about Jaardia, ri trichomonas and the cat would be a useful one to look for, . But may not be necessary to send off faeces for sort of routine, routine culture. We sometimes assess coagulation in patients with inflammatory bowel disease because they have been shown to be hypercoagulable, and occasionally we see them with thrombi or they have thrombotic tendencies.

And the reason is that these dogs, when they're losing albumin, are also losing antithrombin 3, which is a natural anticoagulant. And so then that leads to a prothrombotic state. And as I say, we do sometimes see them present with, with thrombi.

So we quite commonly nowadays use antiplatelet drugs in these dogs, so, clopidogrel. You know, we occasionally see dogs that referred in that have had serum, antigen specific IGEs measured and come back with a, you know, a whole host of things that the dog may be, may be reacting to. There's not lots of good data.

There isn't good data really in the literature to support the measurements of these, antigen specific IgGs, you know, via a, via a blood test. So yeah, once we've done some clinical pathology and plus or minus faecal analysis, particularly looking at things like jaria and the cat tri trichomonas, then we're gonna move on to do abdominal imaging. And as I mentioned to you, ultrasonography is likely to be more beneficial than radiography.

And you may see certain things that suggest a specific disease, so the mucosal striations I alluded to, alluded to before, you can see in animals that turn out to have lymphangectasia. You know, if you find abnormal organs within the abdomen, enlarged organs like the lymph nodes that we found in Josie, it'd be important to do a fine needle aspirations of those, but fine needle aspirating the gut is, is probably of limited value. It's generally non, it's generally non-diagnostic.

You should, . You know, definitely think about the ways to take, take biopsies, and we've touched on this at the moment, but, you know, upper or upper and lower, knowing that many animals have, disease of of both their upper and lower intestines. Including ileal biopsies are probably quite a good area of the gastrointestinal tract to sample if you can, so you have to do that sort of retrograde going via the colon and via the ileocal junction.

And that's probably the best place to find evidence of lymphanicasia is in the, in the ilium. That statement might be a bit too, a bit too rigorous. I think you do, you do find evidence of lymphaia tasia in other parts of the gastrointestin small intestine.

But again, the issue with endoscopic biopsies is they are very superficial and so you miss, you miss things, you miss lymphari taser, you miss inflammation, you miss tumour. So yeah, there's animals that got deeper lesions, particularly lesions in the muscularis or serosa. You probably not gonna pick those up by taking very small superficial endoscopic biopsies.

And, you know, you're going to try and take several from different parts of the intestine, avoid all costs by seeing the large intestine, you shouldn't do that. But, you know, duodenum, dunum, ilium, plus or minus stomach if indicated. People often think that lower blood albumin is a, a significant risk factor for intestinal suture dehins, but it, it's not necessarily been shown to be the case.

So this publication from a number of years ago, available in the Journal of Small Annual practise looked at complications post full thickness intestinal biopsies in 66 dogs. It's not a benign procedure as you will clearly know, but there's no sort of, you know, consistent predictors of, intestinal wound breakdowns, including lobo albumin, so it's not an absolute contraindication for taking intestinal biopsies. You know, you do have to be careful about anaesthetizing period.

Patients with low blood albumin cause, you know, many of the drugs we use are protein bound and things, so, you have to be, maybe careful about drug, drugs that you select and then selecting the most appropriate, appropriate dose. So these dogs, you know. Not all of them had significant by any means, not all of them had significantly low blood albumin, so I suppose that's the, that's the caveat with this, with this study and some also had concurrent diseases like skin disease.

But, you know, there were some dogs that died postoperatively, but again, there is nothing that necessarily suggests causation with things like low blood, blood albumin, so. You know, by all means do intestinal biopsies from animals with low blood albumin and just be a bit extra, extra careful. To be honest, what we might do nowadays if we're worried about significantly low albumin, particularly if an animal that's developing effusions, is to give that patient human albumin, so you can get.

In albumin solution in in bottles. It's about 100 mL litre bottles, and there's various equations that you can use to calculate how much you should give to increase the animal's albumin from the baseline level, more towards the normal, normal level. So it's a very useful, very useful thing.

You should only ever give it once because it's, on repeated administration, you can have anaphylaxis because animals will produce antibodies to the foreign protein that's in, human albumin. And then so we're doing some clinic pathology, faecal analysis, we're gonna move on and we're gonna do, . His, imaging and then biopsying and then, histopathology.

And luckily nowadays there's some good classification systems and sort of, excuse me, templates that help pathologists to give you a sort of uniform nomenclature for various different, different diseases and the, and the severity of those diseases. But imaging maybe didn't dwell on imaging too much. Ultrasonography is super useful.

Yes, you might see changes like, those of lymphaectasia, but, you know, you're looking for, you know, loss of wall layering, which is more likely to suggest tumour, particularly lymphoma, if it's diffuse, then also thickening of the gastrointestinal tract, because that's gonna to suggest pathology, and you need to try and sample that that pathology. So how do we manage cases of inflammatory bowel disease? Well, for me, it's sort of influenced by the severity of the disease and you can tell that by the severity of the clinical signs.

They're serum albumin, so patients with more severe disease tend to get lower serum albumin, so the PLE cases, those are generally ones that have actually got, you know, more severe clinical signs, but not always. And to a degree, I suppose, you know, what type of cells and particularly how severe the inflammatory infiltrates, but for me it's predominantly on clinical signs and also on, on blood albumin. So, you know, animals with dogs and cats with relatively mild to moderate disease, so, you know, they do have clinical signs, maybe of chronic diarrhoea, but they're otherwise, you know, systemically well and healthy and no evidence of ascites, etc.

And that have a normal serum albumin, you might use a sort of a sequential approach like Like this. So, make sure there's appropriate and the parasitic treatments, then maybe a dietary trial or trials, and we'll come on to these individually in a moment. Some people still use antibiotics in case there is a, you know, a bacterial overgrowth, bacterial dysbiosis, leading to inflammation within the gastrointestinal tract.

And if those things don't work, then, corticosteroids should, and plus or minus other drugs should be, should be tried. But those like Josie with pretty severe disease, particularly if they've got protein losing enteropathy and low serum albumin, especially if you've got evidence, you know, of low colloidal oncotic effect by way of fluid accumulation in the abdomen or maybe in the thorax or elsewhere. You should hit them, you should treat them quite hard, so we maybe use, you know, chootherapy with endoparasitics, if we're not sure about the history.

Diet, and corticosteroids, and very, very occasionally we add in some antibiotics as well, but they're generally not, not indicators. And then maybe if they don't respond, then you might need to add in a, might need to add in another drug. So yeah, just a very brief word on, endoparasite treatment.

So, you know, there's not many Endaparasites that lead to diarrhoea and, and chronic diarrhoea. Even fewer in a patient that does have some sort of, you know, relatively regular, sensible antthalytic, treatment regime. But probably the exception because, you know, we don't often kill it with our routine drugs.

It can be difficult, very difficult to find. You're not really gonna find it on faecal flotation necessarily, is, is Giardia, and so you might decide to do a PCR for jardia and you can do that, of course, on, on faecal samples. You know, in an ideal world, to try and identify GRD, you should take faeces from the patient or collect faecal samples.

Successive faecal samples, maybe over 2 to 3 days and pool them, and then send them to the laboratory for testing. That's a good, that's a good way. But, you know, the, the PCRs are relatively sensitive nowadays, so you might be able to pick up jars just from a single faecal sample by doing PCR.

So, you know, either test for and then, you know, if you do identify, treat, or just empirically treat, particularly if there's not a good history of analytic usage, you could just empirically treat with pambenzazole, 550 milligrammes per kilogramme for 5 days is a sort of Giardia treatment regime. Antibiotics, you know, there's a lot of antibiotics. Luckily, Far fewer nowadays, but antibiotics do still get used in patients with chronic diarrhoea.

There's generally no requirement for them unless that patient had a salmonellosis, which is very uncommon, or maybe if you diagnosed Campylobacter and there was, you know, elderly or particularly immuno immunocompromised, owners within the household. Otherwise, at least Kambalo Bacter wouldn't, treat it in, in dogs. So there's a bunch of studies over the years looked at a variety of different antibiotics, to see whether they, can make any many, any difference or not.

. And you know, the earliest studies are really those patients that probably have got that granulomatous colitis thing, but other ones that have had metronidazole, Tylasin, rifampin. You know, it doesn't seem to make a great deal of difference, but thylacin is not used that much in the UK. It is used in some overseas countries, particularly the US.

It's usually a pig or a poultry formulation. But I think the take home for me is that, you know, most of these patients don't require antibiotics. They don't respond to antibiotics and .

Days of rational antibiotic use, I would avoid them unless there's a very specific reason like we've cultured one of the bacteria we've previously talked about. Yeah, well, that note on dietary trials, so, you know, the commercial diets usually contain a whole mix of proteins as well as carbohydrates or other things. And so, you know, historically we've decided, well, we need to find a, a protein that this dog or cat has has never eaten.

Or alternative alternatively to that, we can use a, what's called a hydrolysed diet, whereas you'll remember the proteins in that diet are hydrolyzed, they're, they're broken down, so they're less likely to stimulate an immune response within the, within the guts. And there's evidence for those hydrolysed diets. The issue is that they tend to be less palatable, so, some animals struggle to eat, eat those diets, and particularly if you've got a patient that's, you know, lost body weight and things, you wanna try and maximise dietary, dietary intake.

Other important things, if you're using a diet, the really critical thing, and we see it so, so commonly when it's not done correctly, is the critical thing is to make sure that you stress to owners the importance of them feeding their pet just that diet should have no tidbits, no human treats, no other type of food. Not have access to other animals' food within the household. It's amazing how many times we see patients have been put on a dietary trial, but the owners, you know, feeding some additional snacks or, you know, feeds the dog from the table, whatever it is.

So it should just be that food and. You know, for 4 to 6 weeks, it's, it's pretty rare that animals won't have responded by 6 weeks. And to be honest, most of them will respond if it's a true dietary allergy.

You know, you get marked improvement in the clinical signs usually within the first week or two weeks, but we normally recommend keeping going for about 4 occasionally longer weeks. And, you know, there's quite a significant portion of animals with chronic, enteropathy. They've got a diet responsive disease, so it's often one of our first go to's.

If you think that the animal could have got a dietary responsive, excuse me, enteropathy, and you try a diet and it's not successful, I would usually recommend trying a different diet because it may just be that you've not selected the most appropriate one. Maybe that's got a protein in the animals had previously. Maybe it's a carbohydrate source that the animals had pre previously.

Well, sometimes there can just be other constituents of the diet that the animal's responding to. So sometimes just to change to a different type of diet. Excuse me, and there's a whole load of different, Diets for dogs and for cats with potentially food responsive disease and, you know, there's none that are necessarily much better than the other, so it's whatever you're used to, whatever you can get hold of.

But I think we've moved away from the days of saying, you know, these animals need a completely novel source of protein. So, you know, the sort of kangaroo and whatever carbohydrate source and. Various fish and other things.

What we probably think is that these animals are just responding to something in the diet. And it's not necessarily a protein, having an adverse response to a constituent of the diet, could be a carbohydrate source, it could be others within the diet. And so, you know, the act of changing to a different diet that may not have this certain substance is the thing that's probably going to make the difference, maybe rather than, you know, trying to select a specific protein that that dog or cat has never come across in its life, because that's very challenging to do.

So these are just some and this list is, is not exhaustive of some of the dog and occasionally cat diets, some of these you can obtain. Again, there's hydrolysed diets at the bottom there. But what other things could you, could you use?

Well, animals with, you know, severe inflammatory bowel disease and those that have got a concurrent low blood albumin, as we said earlier, should be managed quite aggressively and so you're gonna use antalytic treatment, particularly for Jardia or test for it, or combinations of both. You are then going to ensure that they have a, an appropriate diet, you know, a novel protein, hydrolyzed or other thing that we just talked about, and then you're probably going to give them prednisolone as well, because if you don't do something, their albumin may decrease and decrease, and they may get, you know, significant central nervous system edoema or develop pleural effusion or whatever else can result from significantly low blood albumin. So yeah, low blood albumin you should get on them quite aggressively and by using multiple things.

And so we normally start on prednisolone, usually an immunosuppressive dose. 2 milligrammes per kilogramme per day. And then after about 3 weeks, we might drop it down by 30 to possibly a bit more percent and then maybe after about another 3 or 4 weeks again, we'll drop it down another 30 to possibly 50% and, you know, you sort of aim to get the patient on the lowest affected dose possible, which to minimise side effects is probably gonna be every every alternate day.

So, prednisolone is sort of the number one drug, it, it should work in many animals. In large dogs rather than using that 2 milligrammes per metre squared, you should consider the 40 milligrammes. Sorry, in the large dogs, rather than using 2 milligrammes per kilogramme, you should use a milligramme per metre square dose.

So look in the table, convert the body weight into 1 metre squared, and then, times that by, 4, so it's 40 milligrammes per per metre squared. It might just, well it does tend to maybe, slightly underdose them and reduce the side effects, which can be really severe in these, these big dogs. Yeah, and side effects, as I say, can be severe, particularly large dogs, you know, they can get significant muscle weakness, they can ultimately go off their off their back legs.

And so people have looked at other steroids, and, budesonide has been around for, you know, 2 or 3 decades now, it's been historically used in humans with. Steroid responsive diseases to try and reduce the reliance on systemic steroids. So this is a drug that's given orally but is metabolised pretty well completely by sort of first pass through the, through the liver, so you shouldn't have any or very many of those steroid side effects.

But people have looked at this drug in, in a few, few diseases and in a study, a bunch of years ago, now 10 years ago or so, looking at butdesonides. Versus prednisolone for treatment of IBD, there was no benefit to using, budesonide. So, I must say we rarely, rarely, rarely.

I can't think of the last time I've used, budesonide, you know, we use prednisolone, we, we understand it, we know how to dose it, we know what the side effects are, and then, as you'll see in a minute, we also know what to do if the animal is showing very significant side effects. So yeah, these are some other immunosuppressive drugs that you could use, azathioprine. Cramba cyclosporin.

My go to is normally cyclosporin. It can be very expensive in, in big dogs. But, it does tend to be quite effective.

It, it works super quickly. Whereas azathioprine can be very slow to start working, so you don't necessarily have, you know, 1 or 2 or even 3 weeks to wait before it, starts working. And, .

Carrabasil is occasionally used, maybe a bit more so in cats that have a sort of a small cell lymphoma that you're worried they're gonna go on and develop a gastrointestinal tract, lymphoma, and the normal sort of dose for me for, The cyclosporin is 5 mg per kilogramme twice, twice a day. And there's various studies looked at a varieties of these different drugs, often in relatively, you know, small, small cohorts, and this table sort of just summarises a summarises a few of them. So, you know, definitely evidence for cyclosporin, or in the second study, maybe prednisolone and cyclosporin, but I don't necessarily think that that's required.

This is an interesting review from the Journal of Veterinary Internal Medicine again, open, open access, from, yeah, a few years ago now, but it's relatively, relatively current. And it talks about the different, different therapies for inflammatory bowel disease or chronic chronic enteropathies. So it's just worth noting, there's what we call a scoring index for use in dogs that have inflammatory bowel disease, because then you can sort of assign a numerical assign a, a figure which can give you an idea about the severity of their disease and I guess ultimately about the, the prognosis, but maybe we don't have that yet until we develop, until we develop more data.

So yeah, back to Josie, so yeah, I remember she was a dog that had got relatively acute onset, clinical signs, predominantly a progressive diarrhoea, although interestingly, more recently, she, you know, may have been, may have been vomiting as well. And we decided it was small intestinal, we did some bloods, generally unremarkable apart from she's got a protein losing enteropathy. She got decreased albumin and globulin.

We did some imaging, found thickness, increased thickness of the intestinal wall, and then we took some endoscopic samples to send those to the laboratory and the diagnosis that came back was moderate to marked inflammatory bowel disease. And but the issue with her is she had quite severe disease. She had significantly lower blood albumin she had very marked clinical signs, so she's not one that you're going to necessarily want to, you know, use parasite treatments and send away and then use a diet and wait 4 to 6 weeks and then try steroids cause she may well be dead by then.

So we use several things at once. We use prednisolone, we use the novel protein diet, but as I say, a hydrolysed diet, or to be honest, just a very good off the shelf diet can can help. She was given metronidazole, we wouldn't generally do that nowadays, so I would avoid antibiotics in these patients.

And she responded to a degree, there was a bit of a reduction in frequency and severity of diarrhoea. Her appetite increased, which was good, but she lost a bit more weight and her owners were quite unhappy. So we added in to the prednisolone cyclosporin at, as I say, 5 milligrammes per kilogramme twice, twice a day, suspecting that she'd got, you know, significant inflammatory disease and steroids weren't enough, so we needed to further dampen down the inflammation in the gastrointestinal tract.

So yeah, what happened after another 7 days, well, the diarrhoea had actually worsened and the owners said, well, we've spent lots of money and we've not got an answer, and in fact our our dog's diarrhoea is a bit is a bit worse. See what's what have we missed off, what have we not done, what have we not, not measured. Well, this is a critical thing to measure in patients with chronic enteropathies, cobalamine, and to a lesser degree folates, and you might decide to measure TLI in occasional cases too.

But patients become deficient in carbalamine plus and minus folate as a result of their intestinal disease. The issue is then if you don't. If you don't provide cobalamine to these patients, their clinical signs can never, never resolve, and so we use things like oral cobalaplex or injectable cobalamine.

So you can see in Josie the carbalamine was significantly below the reference interval. So yeah, don't forget measuring carbalamine and folate. I rarely do it as a sort of a, You know, a diagnostic thing to say, well, the animal's got, you know, proximal small intestinal disease or it's got ileal disease if it's got low coal I mean, I think for me, more, more useful, it's about saying, well, it is low, whatever the cause, whatever the underlying disease, you know, we must supplement it.

And so yeah, within a few days of starting cobalamine, Josie's faeces had returned to normal, and after about a month she'd got back to a normal weight. Owners are happy and we normally recheck cobalamine after about a month. And for patients that you've managed to control their disease with drugs, usually their carbalamine is returned back to within the reference interval.

If you've not managed to control their carbalamine with drugs, You may need to continue it for longer than that. So, yeah, remember colobaamine, it, it's pretty, pretty critical. So just a brief last few slides, just a brief recap about cobalamine.

It's also known as vitamin B12. It's a water-soluble vitamin, and it's synthesised by bacteria in the large intestine of, cats and dogs. So the site of absorption is in the ilium, so, you know, the colon's too late, so you do actually need a dietary, or dogs and cats need a dietary dietary source of it.

And there's a few important things that are involved in the absorption of carbalamine. There's something called intrinsic factor, which is produced from the pancreas, and it's intrinsic factor bound to carbalamine that allows it to cross the . The ilio wall and ultimately get into the, into the bloodstream.

So it's super important for multiple physiological processes, some of which are listed on there and also as a, as a coenzyme. And it's carbalamine deficiency is, is reported in dogs with chronic enteropathies, and in cats to some degree as well. But, you know, relatively, relatively frequently.

And the reason why these patients become deficient in cobalamine, even though they they're having the normal dietary intake, is because the receptors for this cobalamine intrinsic factor complex have been damaged, those receptors in the, in the ilium. And it's been shown that low carbalamine is a negative prognostic factor in dogs with IBD, stroke, chronic enteropathies, and also exocrine pancreatic insufficiency. So animals with exocrine pancreatic insufficiency become deficient in carbalamine because they are not producing the intrinsic factor from their, from their house, from their pancreas, sorry.

So really critical. And so low carbalamine has been shown in experimental animals and others to have really quite profound metabolic and clinical consequences. So these animals can have, you know, significant weight loss, they can be anorexic, failure to thrive, neuropathy, immunodeficiency, but probably the more critical thing in the context of what we've been talking about is that carbalamine is required for sort of normal andterocy function and particularly for sort of vivilli function.

And so, if they don't have carbalamine, The villa don't necessarily work and so you can have malasorption and, and diarrhoea. So we'll see patients like Josie that have, you know, got a disease and we can manage, try and manage that disease, but their clinical signs don't resolve and they don't resolve until you normalise serum carbalamine. So look out for that and you know, if signs come back again, recheck carbalamine because they may have become deficient in it again.

Very rarely, patients need to stay on long term carbalamine because you can just never quite normalise serum levels, but that's quite unusual. And the other thing is, I would probably also supplement if carbalamine is towards the bottom of the reference interval, even if it's not below the reference interval. Because, it may be that the sort of cellular levels of, of carbalamine are, are not sort of reflected by the serum levels, so, lower than, lower than normal carbalamine is probably sensible.

And then a bunch of dogs with and probably cats as well, although the data's not really there with low carbalamine they've also got low folate, we're less worried to be honest about folate, but still makes sense to. Supplement it and nowadays, we of course we can often in many countries get carbalaplex, which is a carbalamine and also folate, and it's got prebiotic and probiotics in there as well. But you could use injectable carbalamine, but it can be painful and quite expensive.

And then as I say, definitely remeasure cobalamine if the clinical signs return. So just a brief summary, you know, there's multiple causes of animals that have chronic diarrhoea, chronic enteropathies, and IBD is quite a common cause. You need to look out for granulomatous, colitis and boxes in French, bulldogs, probably a staged approach to management is, is sensible and less severely affected cases, so.

Dietary trials and ideally 2 because you might not just have identified the, the most appropriate diet you should treat for parasites if the animal isn't on good antho in tics, particularly test for or treat for Giardia with, you know, about 5 days of fembendazole. Antibiotics are probably not required. There's very few dogs nowadays that we truly think have got, what we call an antibiotic responsive diarrhoea or small intestinal bacterial overgrowth, the older, older name.

Corticosteroids is sort of the first line. It means a suppressive drug, but you might need to use other drugs, and cyclosporin is one that I use and often recommended. And then, yeah, cobalamine deficiency is, is common in dogs with chronic enteropathies and also in cats with chronic enteropathies as well.

So, so measure it in both species, make sure it's got back to within the normal range by the time you stop it. If clinical signs are still continuing of diarrhoea, then you may need to continue supplementing it. So yeah, I hope you, hope you found some bits of that presentation, useful, or was some important take home messages there.

So yeah, thanks very much for listening.