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July 15, 2019 – Dr. Kelly Diehl talks about laminitis with Dr. Janet Patterson-Kane, Morris Animal Foundation’s Chief Scientific Officer. The two cover the disease’s scope, current treatment and new research addressing it. They also discuss what horse owners can do to help prevent this debilitating disease.

00:17 Dr. Kelly Diehl: Welcome to Fresh Scoop, Episode 10: Understanding Laminitis: An Ancient Disease, New Concepts. I'm your host, Dr. Kelly Diehl, Morris Animal Foundation's Senior Director of Science and Communications. And today, we'll talk to Dr. Janet Patterson-Kane, Morris Animal Foundation, Chief Scientific Officer. We hope you're learning some things with our episodes. For those of you who may be new, this is the monthly podcast of Morris Animal Foundation, one of the largest non-profit foundations in the world dedicated to funding studies to find solutions to serious health threats to animals. Founded in 1948, by Dr. Mark Morris Sr., a veterinarian, we've invested more than $126 million in more than 2,600 studies that have improved and protected the health of companion animals like cats, dogs, and horses, as well as wildlife. In each episode, we'll feature one of the researchers we fund or one of our willing staff members [chuckle] discussing their work in advancing animal health. Whether you're a practicing veterinarian, technician, or a student, or just an animal-loving science geek, Fresh Scoop is the podcast for you. You can learn more about us at morrisanimalfoundation.org.

01:38 DD: Okay, on to today's show. Today we welcome Dr. Janet Patterson-Kane, Morris Animal Foundation Chief Scientific Officer. Dr. Patterson-Kane completed her veterinary and PhD degrees at Massey University in New Zealand, which will explain her accent. She then traveled to the United States, doing her postdoctoral work at the Livestock Disease Diagnostic Center at the University of Kentucky, and then her residency in pathology at the University of Florida. After spending a few years as an instructor and head of the diagnostic service at the Royal Veterinary College in London, Janet was an Associate Professor at the University of Queensland in Australia. Janet then moved back to the University of Glasgow, where she was a Professor of Veterinary Pathology and Head of the Department of Pathology. And we're happy to have her now at the Foundation. So, she's settled back in the United States after a lot of traveling around. Much of Janet's research efforts in the past were focused on studying laminitis in horses. And she's going to chat with us today about this serious common and important disease of horses. So, thanks for joining us, Janet.

02:48 Dr. Janet Patterson-Kane: Thank you very much for inviting me, and I'm glad you mentioned that accent, so I hope those of you listening out there enjoy something a little different.

02:56 DD: [chuckle] So to start with, Janet, I mentioned that this was an ancient disease. So, can you define for our audience what laminitis is since many of us may be new to the disease, or for someone like me, it's been a pretty long time since I was in vet school and studied it.

03:13 DPK: Sure. So, if we just think about this very simply, it's defined as a painful condition affecting one or more hooves of the horse. And another important concept is it's actually usually a sign of something going on underneath, in the body as a whole, or it could be something in the body as a whole that's quite obvious, like an infection or some other disease. We'll probably get into that later on in the conversation. If we put this in scientific terms, laminitis is a clinical sign of a systemic disease.

03:49 DD: And tell us a little bit about the history of laminitis and... because my understanding is it's... Ancient disease is a correct description for it.

04:00 DPK: Yes, and it's been documented over thousands of years. Certainly, the ancient Greeks were talking about it. And actually, when people have looked at fossil horses, we see evidence of laminitis in quite a large percentage of them, because when laminitis goes on for a long time, we'll start to see changes in the bone. So it's really been going on for as long as horses have been around.

04:25 DD: Wow. So what led you, in particular, to study this disease? What was it about this disease that really struck you and made you want to focus research on it?

04:36 DPK: It wasn't actually something I went looking for. So I'm actually a pathologist and I'm what's called an anatomic pathologist. And so we do necropsy examinations but a lot of that work involves looking at tissue sections under the microscope. So pathologists do often get a lot of opportunities to be involved in all sorts of projects. I was at the University of Queensland at the time, and there was a very active group there working on laminitis. And somewhat unusually for a pathologist, I had done a lot of work with horses. Actually, very few pathologists have. So they asked me if I'd like to participate in their group, and that's when I really became fascinated by this disease which... It is a really, really important disease in horses.

05:26 DD: Right. And that brings me actually to what... And the next thing I was going to ask you, just about that, which is, can you give an idea of the scope of this problem in the horse world, both to the horses and their owners?

05:42 DPK: Yeah. So there've been a number of studies done around the world, and it does seem to differ. So if we look at the United Kingdom for example, it's been estimated that about 10% of all horses in that country every year come down with laminitis. So that's just a huge problem. In a very large survey that was done here in the States, we're looking at about 2%, but if you think about how many horses there are in this country, 2% is quite a lot. And because it's such an incredibly painful condition, that once it's started, it's so difficult to deal with. That really is one of the largest problems for horse owners. And when horse owners are surveyed, that comes up again and again as something people are really worried about.

06:29 DD: Are there horse breeds that seem to be more predisposed to this condition? I know that all horses can be affected, but again, are there some horses you think of as being classic for developing laminitis?

06:43 DPK: Yes. And that comes down to some of the causes. But typically, those horses that are most prone, and what we think of or what are referred to as, "easy keepers," or, "good doers," or some horses just let some people almost just have to look at some food and they'll put some weight on. And these are the sort of breeds that arose in areas where the food was of very poor quality. So we're thinking about pony breeds, also Arabs, Morgans are mentioned, and we shouldn't forget donkeys either. And that might be why we see more of it in the United Kingdom, where we have a lot of native pony breeds that people are still keeping.

07:27 DD: Okay. So you talked a little bit when... In the first question, when... About inflammatory conditions, laminitis being not an isolated condition but really a manifestation of underlying disease, which, I hate to give away how old I am, but when I was in veterinary school, we really focused on laminitis as... We didn't think that much about underlying conditions. And I remember thinking... For those of us who were in the barn, there was a lot of concern about trauma and standing right as a cause of laminitis. But what is... I know that thinking has changed, so what is the current thinking, a bit about the causes of laminitis in horses?

08:15 DPK: Yes. And this has been just a really exciting development over about the last 10-15 years, so I'm going to reveal how old I am. And I was in veterinary school in the mid-'80s, and really, we were talking about laminitis being the result of some sort of inflammatory or infectious disease. So classically, a mare with a retained placenta or a horse with diarrhea, a horse with some sort of fever, that's how we were thinking about it. And that, looking back, in retrospect, came from the fact that a lot of research occurs in veterinary schools and universities. And those schools tend to run second opinion specialist referral practices, and those practices tend to get a higher proportion of horses with these sort of inflammatory diseases, unlike the more general practice.

09:13 DPK: When this started to be looked at, it was probably between the years 2004, 2007, it was realized that something that was thought to be a naturally significant cause, which is what we call, "endocrinopathic disease," was actually more important. And by that I mean hormonal or metabolic, and more specifically, to do with insulin. When this was then looked at, it was found that about 90% of the cases in UK, Europe, and in the United States are actually due to this sort of disease. So that really caused a huge shift in how we think about it, and it kicked off a whole lot of research that we're still going through now and that the Morris Foundation is funding on this endocrinopathic hormonal disease that is at the heart of most of these cases.

10:06 DD: Right, so... And you're referring to equine metabolic syndrome, which certainly did not exist, really, as an entity when I went through veterinary school. And why do you think... I mean, you alluded to it, a lot of early research came out of institutions. But was this happening, and people just didn't recognize it, or is equine metabolic syndrome becoming more common, or is it just like we just diagnose it more? What are your thoughts about that?

10:40 DPK: Yeah, I think both things are going on. So if we look at the term, "metabolic syndrome," we also hear this when we're talking about people, this is coming up a lot. And it's a good example of horses and people being in the same environment and the same society. So it possibly was going on, and it's increased in importance. And just to define what metabolic syndrome is, it's a collection of things going on in the body that are risk factors. So in horses, it means that the horse is more likely to get laminitis. In people, it means they're more likely to get heart disease or blood vessel disease. So in horses, the things we see with metabolic syndrome are obesity, changes in the blood. So things that we call, "lipids," those amounts change in the blood, they can have high blood pressure, but most importantly, they often have high levels of insulin in the blood. And this was first recognized when a researcher was looking at a herd of ponies and found that those that developed laminitis or had a history of it were those that had high levels of insulin.

11:55 DD: So thinking about that and thinking about this really sea change in how we think about laminitis and what we know about it, can you speak a little bit about how treatments have changed, and how laminitis is currently treated, maybe versus 30 years ago when we were both in vet school?

12:18 DPK: Right. And it's not so much treatment, it's in terms of if we know that 90% of cases are due to metabolic syndrome or related things, because horses that get pasture-associated laminitis, that's an interaction with that metabolic syndrome. We now know that if we monitor insulin, we can find those animals that are at a higher risk of getting laminitis. And we now know that if the horse gets laminitis, we need to find out what disease is behind that, so again, we could look at the insulin level. So we're still... Treatment is not the best way to go, prevention is way better than cure. Any sort of laminitis, no matter how early, is a medical emergency. So even if there's even a slight suspicion of it, you want to get onto it because you can reduce the recovery period from months and months down to days. So treatment is still around giving the horse fluids, making the horse comfortable, trying to control pain, certainly working with a farrier on the hooves.

13:27 DPK: But underneath that, we're thinking, "Well, if this horse has metabolic syndrome, let's get that diet sorted out, let's get that weight off." There has been a lot lately about the inflammatory form, where it's been found that cooling the hooves or the feet down, and I'm going to say it in Celsius, less than 10 degrees Celsius, you can convert that to Fahrenheit, using either ice and water or certain sorts of ice boots. And doing that as soon as possible is actually very useful. So if your horse has some sort of fever or an inflammatory disease, just getting those hooves cooled down is a very helpful thing to do.

14:05 DD: That's really different, I think, than what I was taught. And that's awesome. That I think... As you said, "Prevention is probably the key to this particular disease." So I'm going to circle back a little bit and ask you to tell us a little about your research. And is there a particular project or two that you think was most impactful?

14:30 DPK: Yeah. So when I was at the University of Queensland, I was really there, and a group of people, at the forefront of realizing that insulin was a key factor. So I was looking at the pathology under the microscope of what was happening with these horses when the insulin goes up. And that was a really exciting thing to do because there had been this dogma around the inflammatory form, and no one had really looked at laminitis while thinking about what actually caused it. So I was there really early in this group of people working on it internationally. And it's really pleasing to see how that's gone on.

15:12 DD: What came out of that research that you can point to now that we're down the road a little bit, that you can see and say that some of those recommendations came right out of what we studied?

15:25 DPK: Yeah. And I think it just really changed the way we thought about the disease completely. So one of the most surprising findings, and I'm going to have to digress now and talk about the structure of the hoof, which is really difficult without pictures. So I'm going to try my best. So when we look at our own skin, and we just look at the surface of it, the surface of the skin is made out of a layer of cells that we call epithelial cells. And underneath that is this firmer tissue that's largely made out of collagen protein, and that's where the blood vessels are. So when we look at the horse's hoof, we often think of it as being like a fingernail, but it's not actually like that at all. So if we look at the hoof, we have this outer layer, which is very hard, kind of horny tissue. But deep to that is this really highly modified skin, and that's where laminitis is occurring. So there, the epithelial cells are not just in a layer, they're forming these really highly folded structures. And that gives a high surface area because we've basically got the whole weight of the horse hanging off the specialized skin. And between that, those folded structures made of epithelial cells and the bone of the foot is the collagenous tissue with the blood vessels. So holding that collagenous tissue and those folded structures together is this membrane. Really, really thin membrane called the basement membrane.

16:57 DPK: And the dogma was that laminitis is a result of damage to that membrane so that those epithelial cells pull away from the collagen, and then you get the bone of the foot rotating down, and it can sometimes go right through the bottom of the hoof. So that was the dogma that it was a basement membrane disease. And what we found when we looked at the hooves from horses where the insulin had gone up, and we got to look at samples from horses where the insulin had only really been up for a few hours, is that there was either no basement membrane damage, or very little. And that within the first few hours, the first change is that these folded structures become longer. And actually, the cells forming those structures are stretching. And that was just a complete change in the way that we think. And we know that that change is completely due to insulin being higher in the blood.

17:57 DPK: So we really had something very specific to start looking at when we're thinking about how to prevent laminitis and how to treat it. And getting that accepted in the field as a whole did take some years. There were a lot of publications. We looked at samples over and over again and looked at all sorts of different things. And you can now see in the literature, it's completely accepted. But there were quite a number of years where that was not the case. So science does move quite slowly because people don't really want to change the way they think about things as quickly as the research is happening.

18:33 DD: Right. So did anything surprise you in your research? Were you surprised at this finding when you looked at insulin and you were talking about the basement membrane disruption? Or were you... Was that the question that you set out to look at?

18:55 DPK: No. That was not what we were expecting. We almost didn't know what we were going to find. Because when you looked at research that had come before, no one was separating out what the causes were. So they were putting horses with high insulin, as we now know, in with horses that had inflammatory disease and looking at them all together. And so they weren't really getting the whole story out there. I think the other surprising thing was that when you look at these tissues, there's not a lot of inflammation. So "itis" actually means inflammation. This is not really an inflammatory disease, not to look at anyway. And there's a lot of research coming off that now. Looking at why this is so painful, how does the stretching happen, it really revitalized it. Because as we've just talked about, laminitis has been going on for thousands of years, and not really much progress in preventing or treating it. So I think we've gone a long way very, very quickly in this field.

19:58 DD: Good. And I think that was going to be one of my next questions, I think you alluded to, but you can expand on it is, are you seeing people actually using this in your experience? We're a decade later in the clinic.

20:13 DPK: Yeah, absolutely. I think it's more in the prevention. So people who have got groups of horses can certainly look at the ones they think are more at risk, and they can have that insulin measured, and they can monitor that. People are monitoring the body condition score as well because the metabolic syndrome is associated with obesity. So I think there's a lot more awareness because we're going to get a lot further with this by tackling the cause of it, which we really hadn't before, and preventing the stuff, or at least catching it early. Once the hoof structure starts to change, we really don't think it can go back to normal. So this is very much... We're looking at the early stages of the disease.

20:57 DD: So where do you see... As you look at the research that now is going on, what are some really exciting or new avenues that people are exploring in laminitis research?

21:13 DPK: Yeah. And I think... We're looking at 90% of horses who get laminitis have high insulin. And that we really need to get to understand what this connection is because insulin, in order to act, has to bind to receptors on cells. And we don't have insulin receptors on cells in the hoof. So although we definitively know that high insulin causes laminitis, we don't know how that happens, and why, when the insulin is high, those cells are stretching. So there's some really basic scientific questions people are trying to answer. And this often happens when you've got a disease like that and the treatment's not really improving over, in this case, thousands of years, but often centuries with some of these horse diseases. You have to go back to the basic science and find out why it is this disease is occurring. Not to say that metabolic syndrome probably was the main cause for the ancient Greeks. There very well could have been inflammatory or some sort of trauma. So I think this is really exciting basic science research going on on that.

22:28 DPK: But then there's a lot of projects. We fund a lot of projects at the Morris Animal Foundation on metabolic syndrome itself, which is going back still another step. How can we stop that insulin going up in the first place? I know we're funding a project at the moment. We were looking at bacteria in the gut. Do horses with certain sorts of bacteria there, which might be associated with diet, are they more prone to developing metabolic syndrome? Is there something we could do with, for example, probiotics? So really going back way beyond that and just stopping laminitis from ever being a problem. So I think that's really where we're going rather than treatment. It's just going right back there and again, preventing the thing from occurring.

23:11 DD: If you had to pick one message, an important take-home message about laminitis for horse owners and equine veterinarians, what is it?

23:22 DPK: I asked one of my colleagues what she would say to horse owners, and she said, "Don't let your horse get fat." which is probably a fair comment. Although, I should say horses that are skinny can have high insulin, too. So really, it's all about insulin. It's all about high insulin, preventing that from getting high, knowing whether it's high. Monitoring, there are lots of great tools online now to monitor body condition score, getting that down to the level that it should be. There's some great stuff now about exercising, so a lot of these ponies, for example, don't do very much of it. Just monitoring at-risk animals, monitoring insulin. And really, there was a study done where they looked at where the owners were very good at recognizing laminitis. And some people are and some people aren't. So really, if there's any suspicion at all or any sort of lameness, really getting an expert out to look at it and catching this early prevention is better than cure for a disease like this.

24:33 DD: Awesome. So Janet, thanks so much for joining us today and talking to us about laminitis.

24:40 DPK: Thank you. It's always a pleasure to talk about laminitis.

[chuckle]

24:44 DD: So that does it for this episode of Fresh Scoop. Once again, thanks to Dr. Janet Patterson-Kane for joining us. And we'll be back with another episode next month that we hope you'll find just as informative. The science of animal health is ever-changing, and veterinarians need cutting edge research information to give their patients the best possible care. That's why we're here. You can find us on iTunes, Spotify, Google Play Music, and Stitcher. To learn more about Morris Animal Foundation's work, visit morrisanimalfoundation.org. There, you'll see how we bridge science and resources to advance the health of animals. You can also follow us on Facebook, Twitter, and Instagram. I'm Dr. Kelly Diehl, and we'll talk soon.