Dr. Korzenik: One thing that is very important at the beginning to get straight is that there’s a difference between IBD and IBS. Irritable bowel [syndrome] and inflammatory bowel [disease] are two different things.

So what’s the difference between these two things? IBD, as the name suggests, is that there is inflammation, inflammatory bowel disease. And the two large groups in this are ulcerative colitis and Crohn’s disease. IBS is irritable bowel syndrome. It’s a different process altogether. Typically, it’s when somebody’s been fully evaluated, and there’s been evaluation of the intestines and the colon, and biopsies have been taken, and there’s no abnormality that’s detected. So there’s no inflammation there, but still the person has symptoms that may seem like inflammatory bowel disease. Somebody might have diarrhea, alternating with constipation. There may be abdominal pain, typically relieved with going to the restroom. And overall, it seems to be an increased sensitivity of the nerves in the gut to different sensations.

It gets more complicated because there can be an overlap between the two, but predominantly it’s important to keep these things in mind that they’re two separate things and a lot of people say, “Oh, yes, I’ve got a family history. My mother had a history of irritable bowel syndrome.” That’s a little different. [Medical editor's note: You can have both IBD and IBS at the same time.]

Dr. Korzenik: Now, IBD, inflammatory bowel disease, there are more than 1 million cases estimated in the United States, and maybe that’s an underestimate. There’s a study going on now that will give us better information. It’s roughly [split] 50-50 between ulcerative colitis and Crohn’s. And the peak onset is 10 to 19 [years of age], some put it at 15 to 25 [years old]. It’s something, though, that can happen at really any age. It seems there’s some evidence to suggest that very young children, even below the age of 10, it may be increasing even further.

In Crohn’s disease, perhaps 50 to 80 percent of the time, eventually, [a patient will have] at least one surgical procedure. In ulcerative colitis, even though surgery could be considered a cure, it’s a pretty harsh cure. And as many as 20 percent of people will eventually have surgery for ulcerative colitis, most often for refractory disease, but also if cancer or the risk of cancer is identified.

However, having said this and having said the ulcerative colitis and Crohn’s can really make your lives pretty miserable, people, for the most part, can live normal, productive lives. If people have a recent diagnosis of ulcerative colitis or Crohn’s, this shouldn’t be taken as a devastating bit of news. It’s something that will certainly alter your life in some ways, but it shouldn’t change what your expectations are for your life, what you want to do with your life and how you want to live your life.

Dr. Korzenik: So why is this emerging in perhaps the developing countries, and why is this such a common problem now in the industrialized world? There’s good evidence now that there are a number of things that interact to produce this disease. One is genetics, and we’ll talk a little bit about genetics. One is the environment, and we’ve been able to identify some factors in the environment that are very critical in having these diseases emerge, and all together they converge on the immune system. And the immune system is sort of the pivotal player in creating these diseases and letting these develop. Probably no one of them in themselves would allow it to emerge. It’s all three of them interacting that then lead to this.

In somebody who has a very strong family history or particular genetic variant that we’re just beginning to identify, genetics may be the most common thing. In somebody else, it may be [that] the environment is really the critical player, and some of the environmental factors that we’ll talk about may be particularly strong in one person. And that may outweigh some of the genetic factors so that even some of the genetic factors that have been identified in one population don’t necessarily apply to a different population, and environment may be more important. And similarly, in other folks, the immune system may be the critical weakness.

Now, how do we know that there is a genetic susceptibility to inflammatory bowel disease? Well, we know that there are certain racial and ethnic risks for inflammatory bowel disease. Ashkenazi Jewish people, from Eastern Europe descent, are at increased risk compared to people who are, say, Sephardic Jewish population who are more from Spain and the Middle East. But we also know clearly from patient’s histories that people will often have multiple family members with inflammatory bowel disease in the same family, and the likelihood of this happening just as a random occurrence is unlikely. There are also patterns of inflammatory bowel disease in identical versus fraternal twins, and also in generations, and we’ll talk about that briefly.

When we look at twin studies, this is a very good way of trying to identify the genetic factors because you have two people who are identical genetically who have the same risk factor genetically. And we can see do they both develop the disease and what factors [are in] the environment? Fraternal twins are as different as a brother and sister where they share perhaps 25 percent of the genes, but it is not 100 percent.

When we look at Crohn’s disease, if one identical twin has Crohn’s, the likelihood of the other twin developing Crohn’s is over 50 percent. The likelihood of just fraternal twins who don’t have 100 percent similarity is closer to what you’d expect for just a regular sibling. It’s less than 5 percent. In ulcerative colitis, if one twin has ulcerative colitis, the likelihood the other twin has ulcerative colitis is about 6 percent so that there is a genetic influence that is not nearly as strong as it is as in Crohn’s, but it’s still important.

Now, it’s important to look at this both ways. It means there’s an important genetic factor, but it also means there’s a very important environmental factor. So it means that one twin doesn’t develop Crohn’s while the other one does, and what influences that difference is the environment. What makes that person predisposed to get it may be the genetics, but there’s something about the environment interacting with the gene that then provokes it so that that then emerges as the disease in that individual.

Well, how do we find out about genes? There are a lot of different ways, but it’s an area of great interest right now and great excitement because a number of genes have been identified. This is through huge intensive efforts and getting lots of people to donate their blood and looking at the DNA. I encourage you all to be part of such studies, which are in the process to try to identify genes and understand how they interfere.

Now, one thing I should mention is that these are not simple genes as you might have, say, in hemophilia. You have the gene, you get the disease. This is a little bit more complex, meaning you might have the gene, but it doesn’t mean you necessarily get the disease. It means there are other factors. It may be that the gene modifies how the disease expresses itself. It may be that it affects what type of disease you get, whether you get more fistulizing disease or whether you get more disease in the ileum as opposed to in your colon. But it’s not the determining factor as much as just one factor among a number [of factors].

The first gene that’s been identified is called NOD2 or also known as card15. The name itself isn’t so important, but what is curious is that it seems to be important in allowing the body to recognize bacteria and respond appropriately to it. And this is something that people who have a particular variant with this that their body doesn’t respond to bacteria, at least in their gut, in the way that somebody who has the normal gene. And I should say that even when we say normal or not normal, it’s not as if this is a rare thing. Three to 5 percent of the general population has one of these variants. However, so that means that there may be somewhere between say 10 to 15 million Americans who have a variant of this NOD2 gene. However, only perhaps a third of patients with Crohn’s have this particular gene. So it means that out of that 10 to 15 million Americans with this, perhaps only 200,000 or 300,000, will develop Crohn’s. It means that it’s an important risk factor, so that if you have one copy, that increases the risk over the background population by 1.5 to 4 times what you would have if you didn’t have this. If you had two copies, it’s dramatically increased [to a] 15- to 40-fold risk. And about 10 percent of Crohn’s patients carry two mutated copies, and about a third will carry one. But it’s only one of a number of genes, and there are a number of other candidate genes that have been identified and suggested that haven’t been validated yet, but we’re hopefully just on the verge of a whole host of very exciting discoveries.

Dr. Korzenik: There’s a very important environmental component [to inflammatory bowel disease] as well. [One is] smoking. Other things that can stir up a flare [are] antibiotics and infections. Someone is in remission and doing well, they get an infection, and things stir up. Sometimes getting antibiotics can stir it up. But it can be a little confusing because we often will use antibiotics as well to treat Crohn’s. So it’s not as if you need to avoid antibiotics at all cost. You should avoid infections if you can.

And nonsteroidals, meaning things like aspirin, Advil [ibuprofen], Motrin [ibuprofen], all those things are things that some people with inflammatory bowel disease can tolerate well, but many people can’t. And sometimes it can cause a flare of the disease. Tylenol, acetaminophen is fine. That is not associated with flare of the disease. So if you can avoid it, it’s best to avoid nonsteroidals.

Stress: It’s fine to avoid it if you can, but I haven’t found anybody who has been able to yet. It’s also difficult to say exactly that there is an association between stress and inflammatory bowel disease, but certainly if you talk to anyone with any flare, they’ll say, “Yes,” a certain episode or a certain problem happened within a short period of time of this particular flare. So it’s hard not to deny it.

Diet is something which we need to explore much more. I think it’s an area where there’s clearly an impact, and there’s clearly a factor, but we really haven’t understood that well yet how it is. We know there are certain things such as sugar intake that seem to be increased in people with Crohn’s disease. But having said that, it doesn’t mean that you should feel guilty every time you have a candy bar or can of Coke. Because in studies where people have gone on very low-sugar diets, it hasn’t made a big difference. It’s still though, in the bigger picture, it’s stunning. I [read that] in 1815 in England, the typical per capita consumption of sugar, or refined sugar, was about 6 kilograms. Now, in 2000 in the United States, we’ve gone from 6 kilograms to 70 kilograms per capita per year. So that certainly has had some impact on our intestinal flora. Now, you could say back in 1815 everyone was dying at the age of 30 and didn’t have all these sort of problems we have. So we should be eating more sugar. Somehow, I don’t think that’s the answer. But we have to explore further of questions of where diet fits in, and we can modify that.

Smoking is very interesting in that smoking protects against ulcerative colitis. And it gets more complicated because it’s not just that smoking protects against development of ulcerative colitis. But if you’re a smoker and you quit smoking, then you have a higher risk of getting ulcerative colitis than if you never smoked at all. So [it is] protective, but it’s also a risk. Crohn’s is the opposite. And while there are many similarities between Crohn’s and ulcerative colitis, smoking is one of those where they diverge very strongly. Smokers [have] an increased risk of developing Crohn’s. Smokers tend to be less responsive to most [Crohn’s disease] treatments. And smokers have a dramatically faster recurrence of disease after surgery. So if you are a smoker and you have ulcerative colitis, it doesn’t mean that you should continue to smoke. And it doesn’t mean if you have ulcerative colitis and you’re not a smoker, you should start smoking.

There is one patient who I saw a couple of weeks ago who was the most dramatically responsive to smoking I’ve ever seen. And this guy can sort of turn on and off his disease activity by smoking. If he has a flare, he starts smoking again, and within a week he’s back in remission. That’s very uncommon. In most people, it’s sort of a milder impact. There have been a number of studies using nicotine patches to treat colitis, with modest benefit, and people are actually looking at nicotine enemas and a delayed-release nicotine pill. Why it makes this difference we don’t really know, but if you’re someone with Crohn’s, it’s very important to quit smoking. If you’re someone with ulcerative colitis, it’s still important to quit smoking, but you shouldn’t quit when you’re in the midst of a flare.

Dr. Korzenik: What really causes IBD? And the unsatisfactory answer is we don’t really know. It’s not like we can say that there’s a particular bug or bacteria or particular thing that causes it. It doesn’t mean though that we don’t have a very good idea of a lot of what goes on in the process.

So what we think happens is that in the normal gut, there’s this intense interface with bacteria, and there’s some mild inflammation. Your body is trying to protect you from a potential invader, and in the normal, healthy gut there is a little bit of controlled inflammation. Whether you go to some picnic, you eat something, and you get sick. And then everybody who is healthy will then have successful control of inflammation. In somebody with inflammatory bowel disease, there’s a state of sort of unregulated or continued inflammation. But what’s really causing it? We don’t have that down. There are theories. But we have also defined much better what goes on in the inflammation, the nature of the inflammation. But in terms of the fundamental understanding, it’s the idea that in this intense interface with bacteria, your gut system, your immune system in your gut, which is there to try to protect you, has gone a little haywire, and there is an excessive inflammatory response.

Dr. Korzenik: Let’s talk about how we diagnose [inflammatory bowel disease]. Now many of you know this from personal experience. You first go in, you sit down with a doctor or nurse, nurse practitioner, and they take a good clinical history. And that’s perhaps one of the most important things that can be done. So all the information that you can gather and think back on how you’ve been doing, what you’ve been doing, is very important. Physical examination tells us important information as well, and we’ll go over some of that. You have laboratory tests, things like blood counts, and liver tests, and all sorts of other things that give us some insight into what’s going on with your body and what things we have to look out for; what things are deranged, what things aren’t quite right, and these can all be important clues.

Getting down to whether there’s inflammation, we want to see it and want to get a biopsy and be able to look at it under the microscope, and that comes down to the scopes that hopefully, for most of you, are not painful exams. [These scopes are] not necessarily pleasant things that you look forward to, but hopefully things with the anesthesia and various things we have these days [it] should be pretty comfortable and relatively easy. There are X-ray tests. There are a variety of other things, but ultimately when we think about inflammation, we want to get tis sue and be able to identify the type of inflammation you have and help make diagnosis by putting all of these things together and coming up with a final answer.

Colonoscopy in inflammatory bowel disease, this allows us to really look right at it. Now, a lot of you have probably seen the capsule and think, “Oh, boy, is this going to liberate me from having to have a colonoscopy?” Well, unfortunately, not exactly. The capsule is a really remarkable miracle of technology, and it’s a little thing that really is just a capsule-sized thing [that] you swallow. It’s got a camera on it, and you wear a belt, and it picks up the waves. And it can give us important pictures. People with Crohn’s who particularly would want to do a small bowel follow-through [X-ray exam where you swallow barium] first to make sure that that capsule isn’t going to get stuck in a particular place. But this gives us direct images of the entire small bowel. When it gets to the colon, it isn’t so good. They’re working on things for the colon. But, ultimately, the problem is with inflammatory bowel disease. For the most part, we want to get tis sue. We want to be able to get that biopsy and look at it under the microscope to tell us more than just looking at it [with the naked eye]. So, for some people, in some ways this may be helpful, and it may also help identify areas of disease activity that aren’t evident through the other ways that we investigate. So sometimes a small bowel follow-through, the barium that you drink down, may not show everything, and this capsule can be more sensitive. But in addition to trying to assess whether the disease is active and what type of disease you have and where it is, the scope can be very important for surveillance for cancer. People with chronic inflammation with ulcerative colitis and Crohn’s have an increased risk for cancer. One of the important ways of detecting this is through scopes and taking numerous biopsies.

Dr. Korzenik: To give you a little bit of a history in ulcerative colitis; way back in the beginning, diet was really felt to be a chief thing, and particularly there was the thought that it was an allergy to something [such as] milk and wheat. There were a number of bacteria that were brought up, and there was a fad for a while of giving different types of vaccines that were thought to help. At the Mayo Clinic, they had a vaccine that was thought to be quite helpful. And then back in the 1930s, there was a woman in Scandinavia who was approached by the king of Sweden whose mistress apparently had arthritis. And he asked Nana Swartz to develop something to help for her arthritis. And she came up with this combination of a sulfapyridine, a sort of proto antibiotic, which is not really much of an antibiotic, and a proto aspirin, which fortunately is not much of an aspirin. And it helped her arthritis. They then used it in lots of people with arthritis, and they found that in people with colitis and arthritis it helped their colitis. And that was really the sort of mother of all of what we call mesalamines, and we’ll talk about that in a little bit shortly. Cortisol or cortisone steroids were then developed in the 1950s, and then 6-mecaptopurine or something that’s also derived from azathioprine or Imuran, 6-mercaptopurine or Purinethol, was begun to be used in 1962, [which was] really placed more fully on the map by Dan Present in a landmark paper in 1980.

It was found in the 1970s that the sulfa part of it may not be necessary or may not be the key component to help with colitis, and that the sulfa part of it can cause allergies in as many as 30 percent of people. So the problem is that sulfa carries, acts as a chaperone to bring things down to the colon. If you don’t have that, it gets absorbed very rapidly, so a number of ingenious chemists have developed ways of bringing the active ingredient down to the colon or elsewhere in the intestine that you want it to be without the sulfa part. And so those are the medications that we’ll talk about such as Asacol and Pentasa and Colazal and Rowasa.

Steroids are still used. We try not to use them for long periods of time. Azathioprine and 6-MP or 6-mercaptopurine [are used]. And mesalamine is still a treatment foundation for ulcerative colitis. But treatment for all of these diseases is really going through very rapid changes now as some of the new biologic medications that we’ll talk about have come into greater play.

Dr. Korzenik:One of the things about ulcerative colitis is curious is that when it starts, it can be sometimes just a little bit here, sometimes it can be the whole left side, or sometimes it can be the whole colon, but you won’t have just a patch over here. It’ll go here, it’ll go a little bit further back, or it’ll be all the way around. But once you get to the, let’s say, beginning or end of the colon, depending on your orientation there, it doesn’t go into the small intestine. That’s where Crohn’s will sometimes show itself. Ulcerative colitis just affects the colon. It always starts on the left side and works its way back [from the rectum backwards to the end of the colon called the cecum.]

At presentation, there is a small percentage of people who have horrendous activity right from the get go, and those can be very difficult to control. There is a small group of people on the other end of the spectrum who have very mild disease [that is] easily controlled. It still has a presence, but [it is] easily controlled. And the majority of people are in this middle group. It’s not a mild nothing thing, but it’s not horrible. It’s more of sort of what we think of as sort of walking wounded. It’s not a pleasant thing, but they can get along but need definitely something to get them better.

Dr. Korzenik: What are the symptoms? One of the hallmarks of this disease is rectal bleeding and a sense of urgency. If you don’t get to that restroom right away, you’re going to have an accident. And that, in part, occurs because of the inflammation. Our brain is told that we have to go to the restroom when there is a little bit of distention. And when there’s inflammation down there, you don’t have a lot of time and you have more of a sense of real urgency. Diarrhea, needless to say, is one of the hallmarks as well, and abdominal cramping. Pain, as we see in Crohn’s, is a little bit less common, but cramping, particularly around the time when you have to go to the restroom, is really dominant.

Now we think of these things as intestinal diseases, but they’re really also systemic diseases. So they affect a lot of other parts of the body. Joint pain and swelling, [occurs in] perhaps 40 to 50 percent [of patients]; eye inflammation in perhaps 5 percent; skin lesions in 5 to 10 percent. So all sorts of other things can go on in inflammatory bowel disease, and it’s important to recognize that if something else develops, not to think, “Oh, now I’ve got another problem,” but it’s probably all part of the same process.

Dr. Korzenik: When we look through our scopes, what is it that we see? The normal appearance is a little bit like the inside of your cheek. There’s sort of a very nice lacy network of blood vessels that you can see on the surface [of the bowel wall]. It glistens a little bit and looks healthy. Mild disease, the first thing we lose is that nice little lacework of blood vessels. It becomes a little blurred, harder to see. It can be very red and beefy and gets a little bit swollen, inflamed. And then we go to this, which is much more severe, ulcerations and spontaneous bleeding. It’s really much more of a nasty sort of raw meat-type appearance.

What can happen otherwise in ulcerative colitis? Well, the things that we worry about most are sort of the catastrophic things - so a perforation or small hole in the wall that then makes the contents of the gut leak out. Everything outside the gut should be sterile. So if you get all these bacteria in there, you get severe pain, peritonitis, abscesses, inflammation that can be pretty devastating and really an acute, immediate crisis.

Less severe can be bleeding, but still you can get, and in a few percentage of people, more severe bleeding - not just a little bit of bleeding when you go to the restroom, but you’re really pouring out blood and it’s more of an acute, severe bleed. The things that we worry about also are cancer and a stricture. A stricture is something that happens quite commonly in Crohn’s disease. But in ulcerative colitis, it’s rare. And when it does happen, we worry that that could be an indication that there’s cancer there. So that sometimes even when we can’t identify cancer but we see a stricture, we have to make the difficult decision whether someone has to get their colon out, even though we can’t identify cancer but just because there’s a stricture, and particularly a stricture on the left side, there’s an even higher risk of cancer.

Dr. Korzenik: Crohn’s disease is different. Crohn's disease can occur just in the colon in perhaps 20 percent [of patients]. But even when it’s just in the colon, it’s usually not that same sort of confluence that we see. You can have a patch here in what we call the sigmoid, and you may have another patch over here. It’s not necessarily the whole colon that’s involved. About 70 percent of people with Crohn’s will have some involvement of their ileum [the last part of the small intestine]. Perhaps 20 percent will have involvement of their duodenum [the section of intestine that is immediately after the stomach] or higher up in their small bowel, perhaps about 5 percent will have in their stomach, and perhaps 1 to 2 percent will have their esophagus even, and perhaps that’s underestimated.

So it can really be anywhere. But once you have it, that’s pretty much where it’s going to be. It doesn’t mean that you have it, “Oh, no, no, no, I’ve got it in my colon. Now it’s going to pop up somewhere else in my small bowel.” Usually, it sort of declares itself and says, “This is where I’m going to be.” When you have resection [surgical removal of a part of the intestine], if you do have resection, when it recurs, it usually recurs at the site of the resection for reasons we don’t know. It’s usually on the side nearer to the mouth in that resection. About 20 percent of the time it’s going to be in the colon, and sometimes we really can’t tell the difference between ulcerative colitis and Crohn’s.

Crohn’s, the symptoms are similar [to ulcerative colitis symptoms]. Diarrhea is certainly there, but about 10 percent of people with Crohn’s won’t have diarrhea. So sometimes, particularly in kids, you might not have diarrhea, and it takes a little longer then to identify what the problem is. [Other symptoms may include] abdominal pain, tenderness, loss of appetite, weight loss and fever. Fatigue is a really important and major symptom for these diseases. And so often, somebody might be feeling all right, except fatigue is really a dominant problem, and that may be one of the only signs or symptoms that you have that your disease is getting active. Rectal bleeding, ulcers, and particularly in kids, stunted growth [are other possible symptoms].

Sometimes we can tell the difference, and there’s one gastroenterologist who says, “I used to be able to tell the difference between Crohn’s and ulcerative colitis by looking at it with a scope until I learned more.” Once you learn more, you realize you can’t really tell the difference many times between the two. So with Crohn’s, we do tend to see even though the name ulcerative colitis sounds like, “Oh, I should have ulcers all around my colon,” it tends to be more red, beefy. It’s only in the much more severe ulcerative colitis do you see the ulcers. In Crohn’s, though, we tend to see more ulcers. You get this cobblestoning, where you get sort of nubs of more normal tis sue in between all these different ulcerations. Also with Crohn’s, particularly where there [are] areas of chronic inflammation, you can get these strictures, which can cause pain and all sorts of other problems.

With Crohn’s, as with ulcerative colitis, there’s an increased risk of cancer. There’s an increased risk of colon cancer. If you only have your small bowel involved, then the risk of colon cancer is not increased. Crohn’s differs from ulcerative colitis in that you can develop something called fistulas. A fistula is a connection between two open spaces, so it’s sort of a like a straw that goes between two spaces. You can have a fistula between two loops of bowel. You can have a fistula from a loop of bowel to your bladder, from your rectum to your vagina and from the bowel out to the skin. So these are all different types of fistulas, and that’s one thing that can happen in Crohn’s as sort of an inflammation or infection sort of burrows its way along and creates a little sort of like a worm burrowing its way through into the next structure that it gets to. And this occurs particularly around the rectum and can weep pus and cause all sorts of troubles that can be extremely unpleasant, painful and inconvenient. Typically, they arrive from the anus. Sometimes it really starts first as having an abscess, which is just really an infection in a closed space, and then it breaks out here and then you have a little flow. Sometimes it’s just going to be pus, and they are very small openings. Sometimes they can be big enough so that actually stool will drain from there. And they can be quite difficult sometimes to control.

As mentioned, IBD involves not just the gut - skin, eye, bones and joints, and the joints are one thing that can cause pain. Bones don’t necessarily cause pain, but they can be affected from the ravages of steroids. But even if you have never been on steroids, some people with Crohn’s, less so ulcerative colitis, can have some thinning of the bones, and that should be checked in all people with inflammatory bowel disease. There are some kidney complications, kidney stones and other things. And there are different types of liver disease that can occur, both with gallstones, but also other types of things. One such thing is primary sclerosing cholangitis, or PSC, that can affect the liver, particularly in people with ulcerative colitis.