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Interviewer: Diagnosing inflammatory bowel disease, or IBD, that's next on The Scope.

Announcer: Health information from expects, supported by research. From University of Utah Health, this is TheScopeRadio.com.

Interviewer: Dr. John Valentine is an expert at treating inflammatory diseases of the intestinal tract, including inflammatory bowel disease, or IBD as some people know it. First of all, is there a difference between irritable and inflammatory bowel disease?

Dr. Valentine: Those two get confused quite often.

Interviewer: Okay.

Dr. Valentine: So irritable bowel syndrome is quite common. It is not inflammatory, can give you abdominal pain, cramps, diarrhea, or constipation. But inflammatory bowel disease is an immune-mediated process that causes inflammation in the GI tract that can result in similar symptoms, abdominal pain and diarrhea. But because of the inflammation, it can also lead to bleeding in the GI tract, fevers, and complications such as development of cancer if there's long-term inflammation, and the need for surgery.

Interviewer: So it's a little bit more of a nasty character?

Dr. Valentine: Yeah, I agree.

Interviewer: Yeah, okay. So I hear that inflammatory bowel disease is actually increasing quite a bit. Can you talk to how much?

Dr. Valentine: Well, it's increasing in both western countries, and then in countries that are now westernizing. China, India, South America are now starting to see an influx of inflammatory bowel disease and exactly why isn't clear. But because patients are diagnosed very young and we can't cure it, we can treat it, these patients are living with it. With the increased rate of new cases, some predictive modeling suggests that the number of people living with inflammatory bowel disease in North America will double in the next 10 years.

Interviewer: That doesn't sound very enjoyable for a lot of us, then.

Dr. Valentine: Well, fortunately, we have multiple treatment options. We can treat this, but we can't cure it.

Interviewer: All right. In another segment, we'll talk about treatment options for IBD. Because from what I understand, there's quite a few of them and it's probably worth its own particular podcast. So take me through the process that you'd use to diagnose someone's IBD.

Dr. Valentine: Well, typically a patient would come in with chronic symptoms. An infectious colitis, for example, of Salmonella, Shigella, the common bacterial infections, you may have similar symptoms, but they'll only last three to five days. If somebody comes in having blood in their stool, loose stools, maybe fevers and it's been going on for a couple weeks, then we start thinking about inflammatory bowel disease. Which we then need to differentiate between ulcerative colitis, which only involves the lining of the colon, and Crohn's disease, which can be anywhere in the GI tract, but tends to like the end of the small intestine, first part of the colon.

Interviewer: Are the symptoms for all those the same? Or do you use a little bit of a different diagnostic then to figure out specifically what somebody might be dealing with?

Dr. Valentine: Well, there is a tremendous overlap between the two. Where the inflammation is can make a big difference. If your inflammation is only at the very end of your small intestine, you may not have diarrhea at all. Where if the inflammation is in the rectum and lower part of the colon, then diarrhea and visible blood would be a more common feature. So we can get some hints as to which one we think it is, but we need to do some more diagnostic testing to straighten that out.

Interviewer: In addition to symptoms, are there other risk factors that you ask the patient about to help determine if that is indeed what they have?

Dr. Valentine: The risk factors don't exclude it, but it certainly increases the probability.

Interviewer: Okay.

Dr. Valentine: So the biggest risk factor we know for having inflammatory bowel disease is having a family member who has it. That being said, somebody needs to be first. But there's often a cluster of other immune-mediated diseases in the family, multiple sclerosis, rheumatoid arthritis, lupus or celiac disease. These are all different diseases that do share some genetic underpinning so that's why they tend to cluster together.

Interviewer: Do you find that patients do a pretty good job of self-diagnosing by the time they get to you?

Dr. Valentine: It depends. If they have a family member, especially a brother or sister with it, yeah, they know what the symptoms are and they come in, "I think I sort of have this." If they're the first in the family, they really don't know.

Interviewer: Okay. So what are some of the other diagnostics that you use to determine for sure if they have inflammatory bowel disease?

Dr. Valentine: Well, the number one cause of bloody diarrhea is infection so you always need to rule out infection. Sometimes, though, the infection can be the trigger. We treat that, but the inflammation won't go away.

Interviewer: Okay.

Dr. Valentine: So we have to rule out infection. The patient's age also can give you some hints.

Interviewer: Okay.

Dr. Valentine: So ulcerative colitis and Crohn's, they're a peak onset stage of 15 to 25. It can occur a whole lot younger. It can occur in the 60s. But a 25-year-old coming in with diarrhea for several weeks with blood in it, inflammatory bowel diseases goes to the top of my list.

Interviewer: Are there any tests or screenings that you use?

Dr. Valentine: A colonoscopy would be the primary diagnostic test. You want to be sure you know what you're treating, especially because some of the treatments involve immunosuppressant medications. So a colonoscopy, make sure you know whether it's ulcerative colitis or Crohn's. Make sure the pathology, what the pathologist sees under a microscope fits with that diagnosis and not some other bizarre or much less common etiologies.

If the colonoscopy doesn't reveal any problems, then imaging of the small intestine, and there are several ways of doing that. An MRI or a CT scan would be most common. Occasionally, the capsule endoscopy, but I'm really wary of people who get diagnosed based on images from a capsule endoscopy by itself.

Interviewer: Why is that?

Dr. Valentine: Lots of things can cause inflammation in the small intestine. Little discreet breaks could be caused by taking ibuprofen and similar types of medications. So when they even show these pictures to the experts, they have a hard time deciding what might be due to these ibuprofen-type medications and what might be due to Crohn's disease.

Interviewer: At this point in our conversation, if somebody is convinced at this point that they have inflammatory bowel disease, would they go to a general practitioner or their primary care physician first? Or come straight to you at this point?

Dr. Valentine: Well, like I said, need to exclude infection. So I think going to the primary care doctor to get the stool studies done to exclude Clostridium difficile infections, Salmonella, Shigella, campylobacter, the other bacteria that can cause inflammation in the colon would be the first step.

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updated: April 17, 2019
originally published: March 15, 2016

Interviewer: Donor matching for fecal transplants, we'll talk about that next on the Scope.

Announcer: Examining the latest research and telling you about the latest break throughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. June Round, assistant professor in pathology at the University of Utah. Dr. Round, I think most people have heard about fecal transplant by now, but how effective are they really?

Dr. Round: So I think people have heard a lot about fecal transplants being for clostridium difficile infections. So they work quite well for this kind of transient infectious organisms.

However, people have started to try them for other intestinal inflammatory diseases like inflammatory bowel diseases, such as ulcerative colitis or Crohn's disease and they are less effective. And I think if we now understand how these microbial communities are shaped will help us to better understand how we can make fecal transplants more effective in the future.

Interviewer: And that's a good segue to your research. You did fecal transplants in mice and got some very different results depending on how they were done.

Dr. Round: So we're working with three different strains of mice, so they kind of represent three different people. But you infect them with the same amount of salmonella, which is now a fairly low dose, something that a human might take from contaminated food and some of these animals would dropped dead within two days.

Interviewer: Oh, my gosh.

Dr. Round: Other animals would live well over a week and actually clear the infection, so the differences between the susceptibility or resistance of these animals is really huge. And of course there was the third animal which had a very intermediate response. They didn't drop dead, but they got very sick, had a lot of diarrhea, but eventually cleared it after a couple of days.

Interviewer: This is just sort of their response before the transplant, is that correct?

Dr. Round: That is their baseline response right before the transplant, that's right.

Interviewer: Okay. And then once you did the transplants, what were the differences you saw there?

Dr. Round: So the animal that was highly susceptible, the one that would drop dead after two days after salmonella infection, if you give the fecal transplant from the highly resistant strain, that susceptible strain now became highly resistant. Meaning that instead of dropping dead after two days, it was able to live for well over a week and then clear the infection. So you can essentially make a susceptible animal highly resistant by simply giving it a fecal transplant.

Interviewer: So what was different about these different fecal transplants?

Dr. Round: The difference between the fecal transplants was that they came from animals that had a different suite of immune genes, and these immune genes are called Major Histocompatibility Complex or MHC, so there's lots of these MHC genes. So express multiple MHC genes and the very different throughout the population.

Interviewer: So maybe a little bit like we have different blood types, but more complicated than that.

Dr. Round: That's a great example.

Interviewer: Do your findings suggest that people with a certain MHC profile will always combat certain infections better than others?

Dr. Round: The major point of our paper is really that your MHC type dictates the type of microbes that live on your body. So some people I have an MHC type that selects for really good robust organisms that help them fight off salmonella really well, whereas other people might select for organisms that don't allow them to fight off salmonella very well. The same could be true for some . . . that's why some people get inflammatory bowel disease, some people don't, is you're selecting for just different cohorts of microbes.

Certain MHC types are associated with certain infections. Now, people always thought that that was because the immune system was presenting a better suite of antigens and mounting a better immune response. That's what has been thought for decades and decades, so our findings suggest that it's beyond that actually, it's that the MHC is selecting for microbial communities and some microbial communities are better at helping us battle infection.

Interviewer: I've been learning about certain companies that are making so called poop pills, where they take healthy donors and offer those as fecal transplants for, I think, right now it's mostly for people affected with the sedate. But what you're saying is that if they did an additional screening step it may help those therapies work better.

Dr. Round: Yes, I think for things like infections where the infection lasts a week, it's a very short time frame. I think that the best thing to do would be take it from a very resistant person, resistant to that particular infection because they probably have microbes that are able to fight the infection off.

In our case we were testing salmonella infection. Now, if you want to think about the broader picture, the implications of our findings, although I will say that we haven't quite tested it, is that perhaps for more chronic diseases like inflammatory bowel disease you might have to MHC match for microbes.

Interviewer: The MHC complex and what it does is the same system for like graft versus host when you donate a kidney for example you have to make sure that you have a match.

Dr. Round: That is exactly right.

Interviewer: And if you mismatch then you reject that graft.

Dr. Round: The one thing that's becoming evident is that you can give probiotics to people. You can give them millions and millions of bacteria in a little pill, but it doesn't always stick in the gut. It kind of gets flushed through. And part of that could be because that person doesn't have immune system that selects and allows for that bacteria to live there.

The same is true for fecal transplants. A lot of times to give a fecal transplant to someone and it works for a little bit, it stays in the gut of those people for a little bit, but then eventually those organisms get either competed out, flushed out, they're just not selected for.

So our findings suggest that perhaps we can make fecal transplants stick a little bit better if maybe we match the MHC donor to a recipient. We keep talking about this idea of personalized medicine and I think as far as personalized medicine is concerned, we're going to have to couple the genetics of the person, which is going to include the genetics, their immune profiles as well.

We're going to have to couple the genetics with the person along with the types of microbial communities. I think if in the future we can put those two together that we can have some really powerful therapeutic interventions in the future.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope, University of Utah Health Radio.