Ms. Present: Welcome to Advances in IBD: New and Current Treatment 2005.

My name is Jane Present. I live in New York City where I've lived all my life. I am married to Daniel Present, who is a gastroenterologist specializing in inflammatory bowel disease.

Advances in IBD is a collaborative sponsorship among eight pharmaceutical companies who manufacture and distribute competing products used as treatment. They have come together to sponsor advances in IBD for patients with inflammatory bowel disease and their families.

I am very grateful to [our first] sponsors, Proctor and Gamble who make Asacol and Centocor who manufacture Remicade [infliximab]. They have been joined by Axcan Pharma who produce the Canasa suppository, Salix, manufacturers of Colazal [balsalazide] and a new drug Xifaxan [rifaximin], and Shire USA who make Pentasa [mesalamine].

And this year, we welcome two new sponsors whose products have not yet even been approved for treatment in Crohn's disease by the FDA. But I believe in keeping all of you up to the cutting edge. So when we talk about these drugs and you read in the newspapers that they have been approved, you will speak with your physicians about them: Abbott Laboratories, who manufactures Humira [adalimumab]; Berlex Laboratories who produces a drug called Leukine [sargramostim]; and a third new sponsor, Protein Design Labs, whose expertise is in clinical trials.

For the past six years, I've been traveling all over the United States. I visited 67 cities in the top 75 markets. Our team has traveled with one of the top thought leaders in IBD as a visiting professor, and we invite two very sharp local gastroenterologists to serve on the panel with us. By the end of [this] meeting, you should understand all you need to know about IBD.

Let me tell you a little bit about how the program goes. The first part of the discussion is focused on the basic facts of Crohn's disease and ulcerative colitis. We want to share with you what the symptoms are, what makes you feel sick enough to go to the doctor, what tests are done to help your doctor arrive at the correct diagnosis. And you will learn how competent physicians are able to conclude that you have IBD.

Secondly, we want you to know about the systemic complications of IBD, that is, symptoms which occur in other parts of your body, other than your gut. And if you don't know to look for them, you can be fooled into thinking they are not related.

And finally, we will bring you up to date on the treatment of IBD, the many possibilities and options available today that were not available, that were unheard of 20 years ago.

However, our imminent panelists do need a little help from you. They need to know how much you already know. So with a show of hands please, is there anyone in the room who has never attended an educational meeting on IBD? Will you please raise your hand? Oh, that looks like most folks. Will you please raise your hand if you are a Crohn's disease patient? Will you raise your hand if you are an ulcerative colitis patient? [There is] a little more UC than Crohn's.

Please raise your hand if you are here in support of a patient who has IBD. Now you guys take your other hand and give yourselves a round of applause. Thank you for being here. It is so important. You should applaud yourself because you are the best, and we're so glad you are here to support your spouse or your child or your parent or your significant other, your friend, in other words, someone you love and care about.

Now, is there anyone here who still thinks their disease would go away if they changed their job, how about change their spouse, got more sleep, ate more sensibly, reduce the stress in their lives? Or heaven forbid, has anybody ever told you that your disease is all emotional, is all in your head? Well, we're going to make certain that if you ever did believe that mythology, you will learn tonight that you have a very real chronic illness. It's called Crohn's disease or ulcerative colitis or some variation of both, which we call indeterminate. And they are not imagined. They are not emotional. They are not in your head, but they do hurt, and they sometimes hurt so bad that you can't get out of bed in the morning.

If you're a youngster, these diseases have caused you to miss school, summer camp, sleepover dates with your friends. As an adult, you may have missed work. You certainly won't take a long car trip without plotting out every pit stop along the way, and it is really hard to share those feelings with those folks who don't get it. So if you're suffering, you're suffering for the most part by yourself in silence. And I also know that you checked out where the restrooms were before you came in the room tonight.

As I said, Crohn's disease and ulcerative colitis are known as systemic illnesses. That means they affect the entire body system. And so tonight, we'll talk about what is called systemic or extraintestinal manifestations of IBD, what you should know to look for, how to manage what you find. For example, you wake up in the morning and your eyes look red, and you think you're having an attack of allergies, pink eye, or pollen reaction. You need to know that it could be a signal that your IBD is about to flare.

That sore on your leg may not be the result of an infected mosquito bite but an indication that you're about to experience a flare. And you probably didn't know because I didn't know that a seemingly harmless antibiotic ointment called clindamycin applied to the skin can actually trigger a flare-up. So you need to know what those signs and signals are and what to look for, and after tonight I hope you will have all of that information.

You may not know that if you're taking steroids like cortisone or prednisone now or have ever taken steroids you may very well be making yourself prone to cataracts in your eyes, weakening of your bones and making yourself prone to fractures. You may need to be on a medication to restore and maintain healthy bones.

Now I will introduce the members of the panel to you in a moment, but I thought it would be fun to share a couple of very old slides with you. And when I say very old I mean very old. The first slide is that of old Burrill B. Crohn himself. Burrill B. published the very first paper while at Mount Sinai Hospital in New York in 1932. He described an inflammation or narrowing of the lining of the ileum, the small intestine, and he named it regional enteritis.

Sometime later, he changed it to terminal ileitis because the disease occurred, he thought, at the very end of the small intestine, which is referred to as the terminal ileum. Now, I don't need to have to tell you that calling anything terminal is not cool. It didn't work, and so he finally changed it to ileitis, which simply means inflammation. Anything with i-t-i-s at the end of it, medical term, means "inflammation of." So this means inflammation of the ileum or small intestine.

There were three names on that first paper, and this is Dr. Gordon Oppenheimer who was a urologist and he died early on in the late '60s. And this slide is Dr. Leon Ginzburg, a very well-known Mount Sinai Hospital surgeon who was the third name on the paper. Leon complained until the day he died that it was he, and not Burrill Crohn, who had done all of the work, and the archives at Mount Sinai seem to indicate that he was right. Only in those days, published papers were done in alphabetical order, and Crohn's name started with a "C" and Ginzburg's name started with a "G," and so it was called Crohn's disease.

Now, Burrill lived a very long time. On the right, this is a slide of him on his 99th birthday. Leon Ginzburg is standing next to him, and that devastatingly handsome fellow on the left is the father of my three perfect children and grandfather of our four perfect grandchildren.

The history of research in Crohn's disease starts at Mount Sinai Hospital in 1965 where the name became Foundation for Research in ileitis, Inc. After two years, one of the imminent thought leaders suggested that since the symptoms were so similar we should include ulcerative colitis. And we also got a second chapter, I think it was in Brooklyn, so we gave ourselves the privilege of calling ourselves the National Foundation for Ileitis and Colitis, Inc.

In 1990, when I was fortunate enough to be serving as president of the organization, I realized that people couldn't find us in the phone book, and so we needed to be up there. By that time, they'd stopped calling it ileitis, and they were calling it Crohn's disease. And so against a lot of problems with the founders of the organization, we changed the name to the Crohn's & Colitis Foundation of America.

And this is a slide taken in 1965 on the day that research began at Mount Sinai. It may be the only time that these three gentlemen were photographed together. The rumor was they didn't like each other very much. And it shows a generous donor handing a check for $25,000 to the very famous Dr. Henry Janowitz to start research in inflammatory bowel disease. That was Oppenheimer and Crohn and Ginzburg all together, the first and only time.

Let me introduce the panel to you. Dr. Rick Sigmon is making a comeback visit. He was here six years ago when we were here. He is a panelist to whom you should address your questions about your child's IBD. Rick is a Tarheel, born in Hickory, North Carolina, graduated from UNC, [where he completed his] undergraduate, medical school, internship, medical and pediatric and medical residency, gastroenterology and pediatric GI fellowship. Rick practices pediatric gastroenterology at the Carolina Digestive Health Societies here in Charlotte.

Dr. Michael Gaspari hails from up north in Reading, Pennsylvania. He graduated from Franklin and Marshall College in Lancaster, Pennsylvania and Hahnemann Medical College in Philadelphia. In 1981, he journeyed south to North Carolina Baptist Hospital and the Bowman Gray School of Medicine in Winston-Salem as an intern, and he stayed for two additional years to complete a medical residency. His GI training was completed at the Medical College of Virginia in Richmond. Dr. Gaspari practices at Carolina Digestive Health Associates here in Charlotte. He carries the academic title of clinical assistant professor of medicine at UNC and is affiliated with Presbyterian and Mercy Hospitals, Carolina Medical Center and Union Regional Medical Center in Monroe.

Tonight's visiting professor is rapidly rising to become a major thought leader in IBD. That's what I said the first time I introduced him six years ago when he started working with me. Now six years later, it is safe to say he has joined the ranks of the major thought leaders in IBD. He is a superb physician and clinical researcher. Dr. Gary Lichtenstein is professor of medicine at the University of Pennsylvania. He was born in Allentown, Pennsylvania, received a bachelor's degree at [the University of] Penn[ sylvania] and an M.D. from my favorite institution, Mount Sinai Hospital in New York. He then traveled south to Duke University for an internship and two-year medical residency and returned to [the University of] Penn[ sylvania] for a GI fellowship. He joined the staff of the University of Pennsylvania in 1987, and there he has stayed focusing his energy and talent on the study of IBD and putting the University of Pennsylvania's GI division solidly on the map. He was listed as one of the best doctors in America in IBD, and I am delighted that he is able to be here.

Dr. Lichtenstein: Crohn's and ulcerative colitis are relatively common disorders. About approximately 1 million Americans have Crohn's and ulcerative colitis combined. It's about a 50/50 [split between] Crohn's and ulcerative colitis. [There are] 10 new cases per 100,000 people per year, so it's a relatively common diagnosis.

[Inflammatory bowel disease] occurs early on. Age 10 and 19 are the peak ages it occurs. My colleagues at Children's Hospital in Philadelphia have seen a baby as early as three months of age diagnosed with Crohn's disease. So it's very early on that you can get the disease, and the diagnosis is often many years before it's firmly established because it can mimic many things, and invasive tests are required to make that particular diagnosis.

The scope of the disorder is such that it is something that requires visiting a physician in an effort to diagnose and to treat. Seven hundred thousand times a year physicians are visited in the United States regarding inflammatory bowel disease. One hundred thousand hospitalizations [occur]. So it is something that takes a toll on the individuals as well as on the health system.

If you look overall at individuals with Crohn's, 50 to 80 percent of the people will have surgery at some point in the life of their disease. Forty percent or so may have a re-operation when it comes to Crohn's disease. In ulcerative colitis, 20 to 40 percent of people may have surgery, and this may depend on the distribution of the inflammation. In other words, where is the inflammation in the bowel?

Most patients live a normal life. So you're not going to die from your disease. That's the good thing. Crohn's and ulcerative colitis, the life span of people that have Crohn’s disease and ulcerative colitis is very similar to the general population in the United States. It may differ by one year. And that's something that's important to realize. But there are some things that can make you ill, uncomfortable and wish that you didn't have the disease. Certainly that's something that anyone with any disease wishes, but because of the symptoms, which we'll review, this is something that's important.

There's a group of individuals that have an uncertain diagnosis, and it's not because your doctor isn't smart enough to figure this out, it's because your disease isn't behaving appropriately. It's somewhat like Crohn's disease. It's somewhat like ulcerative colitis in features, and because of that we call that indeterminate colitis. About 10 percent of all people with inflammatory bowel disease will have what we call indeterminate colitis.

Dr. Lichtenstein: [In the] United States and Canada, we can see a very high incidence in developed, educated countries, Europe as well. If you look at areas that are less well-developed, you're going to see a lower incidence, in other words, less cases of disease being present. South Africa has more, and Australia has moderate incidence. And, again, that goes along with the education, the hygiene has been thought to be an important issue. Those [countries] that have good hygiene and well-developed sanitary systems may be such that they're doing themselves in to some degree.

That has led to some treatment with a pig whipworm, Trichuris suis, where individuals have ingested the larvae [eggs] of this as a treatment. [Medical editor's note: The worms don’t survive very long in humans.] This is under investigation now because the perception is that individuals [in developed countries] have a very unexposed body to things such as parasites. So the body's immune system - in other words the white cells that come in and attack infections and other abnormalities and are involved in the inflammation in the bowel, which we see in ulcerative colitis and Crohn's - are such that they are not active, and they're not attacking because they've been so clean they haven't had exposure. And that's a theory. [Is it] real? We don't know. But that's something under investigation.

We know individuals that have family members are more prone to get inflammatory bowel disease. If mom has inflammatory bowel disease or dad, the son or daughter has about an 8 percent chance of having inflammatory bowel disease.

The environment is important as well. We talked about the geography but also the environment. So if someone develops an infection of the bowel, they may have salmonella, Shigella [types of intestinal bacteria], anything of these things that you can get from eating food that is tainted.

Now, do all of these [triggers] contribute equally? They may contribute differently in individuals. In some people, you may see genetics playing a bigger role, in others perhaps the environment and in others maybe the immune system may be more active. So this is not saying one size fits all, rather there are individuals and individual change or variation.

Dr. Lichtenstein: So let's talk about genetics - the susceptibility to inflammatory bowel disease. There is racial and ethnic risk of inflammatory bowel disease. For example, the Jewish population is anywhere from three- to eightfold more likely to have inflammatory bowel disease than the general population.

Racially, the Asian population is very [unlikely] to get inflammatory bowel disease. African Americans, years ago, were thought not to be likely to get inflammatory bowel disease, but, more recently, they've been recognized to have inflammatory bowel disease in increasing numbers.

Multiple family members: There [are] some families that I see , [where] a mom, a daughter, a grandmother, a grandmother's mother, going back many generations that had ”nervous stomachs,” but perhaps weren't diagnosed with truly Crohn's or ulcerative colitis. Recently, however, with the advent of the new techniques to diagnosis inflammatory bowel disease, perhaps they recognize [it].

Identical twins: There's no report ever of a group of identical twins where one had Crohn's and the other had ulcerative colitis. So if you have a son who has Crohn's and he has a twin, if he gets inflammatory bowel disease, the other twin, it's going to be Crohn's. So, again, genetics plays a role.

[It is] also important to see in this particular study if you look directly [at] identical twins, fraternal twins or non-identical twins, the likelihood of ulcerative colitis disease presence in the twins [is] 6 percent; 58 percent in identical twins. So that's extremely high directly. And then fraternal twins are very similar with Crohn's disease as in the identical twins with ulcerative colitis. So this is more important in Crohn's than it is in ulcerative colitis.

The academic world has tried for many years to search and find, a “gene,” an abnormal part of the DNA, the codes for making various things, proteins and enzymes in your body.

It's probable that there are many different genes, in other words, pieces of DNA in individuals that are abnormal that have Crohn's and ulcerative colitis. The genome-wide screen is better in families that have multiple individuals that are affected. So mom, dad, maybe generations back will have Crohn's disease. So this looks for evidence of linkage. And I won't go through the specifics, but in case you hear of these or read of these this is important to realize.

And I'll just mention the NOD2 gene. This is the first gene discovered to be abnormal in people with Crohn's. It is represented here in amino acids that make up a protein. Amino acids are the basic building blocks of protein. And it leads to inflammation, and it is abnormal. And this can be measured by taking a blood sample. It is not commercially available, and it should not at present be tested for based upon the information we have.

It does not necessarily predict an individual will or will not have disease, but if you have one copy of an abnormal or a mutated gene you have anywhere from one-and-a-half to four times the risk of having Crohn’s disease. If you have two copies, it's 15 to 40 times that risk.

If you look at the other side of the coin, what about the individuals that do have Crohn’s disease? What is their risk of having any abnormalities? Ten percent of people, one in 10 people, who have Crohn's will have two abnormalities. Whereas, one in four will have one abnormality in the protein, the gene that is present.

Dr. Lichtenstein: If we go back to the environmental triggers directly, we can see that many things come to mind when you think of things that might aggravate someone that has colitis or Crohn's. And there might be infections. So someone that has ulcerative colitis or Crohn's gets an infection, their disease may flare, it may become active. They may get symptoms of disease such as diarrhea, abdominal pain.

Nonsteroidals: Advil, Motrin, Nuprin [ibuprofen drugs], Aleve [naproxen], these are all things that can initiate someone who is doing well to get inflammation to become active.

Stress [can also cause a flare]. Smoking: If you are a person who has ulcerative colitis and you stop smoking, the disease may become active. If you start smoking again, it may go into remission. I don't advocate smoking under any circumstances because of the lung cancer, stroke, cancer of the pancreas, breast cancer, and every other cancer that has been associated with such, but this is something of interest. And it is thought that this may be the nicotine, but we don't know. Crohn's is the opposite. If you smoke and you have Crohn's, you're likely to have more active, more difficult-to-treat disease.

Diet may play some role in people typically that have Crohn's that have narrowing of the bowel. And if they've had surgery, they may be able to eat well. Ulcerative colitis may only be a problem when people have active symptoms. They may be able to eat anything they like when symptoms are inactive. So individuals may vary with diet. It's very important to realize this may vary over time.

Antibiotics taken for other reasons, [such as] respiratory infections, may cause some disease to be active in some people. But you have to look at this and [ask], “Is it more important to suffer from an infection like pneumonia, or is it better to treat the pneumonia, feel well and take a risk of treating the colitis?” So it's not always an easy answer, but you need to weigh the risk against the potential benefit.

Dr. Lichtenstein: What causes IBD? We know the body has inflammation throughout it at all times. It's normal to have inflammation. The bowel has inflammation; there are environmental triggers, infections and when we eat food there is bacteria in the food. The body becomes inflamed to a moderate degree, however the immune system is able to down regulate that, in other words, get rid of the inflammation that is present in the bowel, and you get a noninflamed bowel in a normal individual.

[People] with ulcerative colitis or Crohn's do not have that ability and, therefore, get inflammation in the bowel. Now when they go into remission, have no symptoms of their active disease is what I mean by that, then individuals may get into the state with the lack of inflammation in general.

Dr. Lichtenstein: How do we diagnose IBD? So someone presents with abdominal pain, cramping, bloody diarrhea, that could be characteristic, in other words, individual symptoms that are commonly found in ulcerative colitis. We do a physical exam. In Crohn’s disease, there may be inflammation. We may feel a fullness in the right lower belly where the ileum and the cecum are. We'll talk about the anatomy shortly, that's the area commonly where Crohn's may occur. We might do laboratory tests, we might do endoscopy. Endoscopy means to look in the bowel with a scope, a camera with a light on it to identify the inner lining of the bowel. And that could be the upper digestive tract or the lower digestive tract. That could include the colon or the upper GI tract, stomach, esophagus, small bowel.

The other thing we can do are X-rays, and I'll talk about X-rays and how they're helpful. And we can sample a small piece of the tissue in the bowel, the lining of the bowel, take a biopsy. So these are all important things.

And if we look at colonoscopy, which is looking at the large intestine, the colonoscopy means looking with a scope - then we can diagnose Crohn’s disease or ulcerative colitis. We can see the large intestine and the ileum, the lower portion of the bowel that is not normal in people with Crohn's. That is normal in ulcerative colitis, and we can take tissue and take biopsies. We can see how active the disease is. Is it a little inflamed, is it inflamed [a lot]? Are there many ulcers present?

In individuals that have long disease duration, in other words they've had colitis or Crohn's for many years, [they] are at a somewhat higher risk to get cancer of the colon. Now, I'm not saying everyone gets it by any means. It's a small percentage of people, but it's enough to go to your physician and make sure that you get what's called a colonoscopy done for screening or surveillance. Screening means looking for any abnormalities. Surveillance means once you know you have something to go repeatedly back and have testing done.

You swallow food, it comes down into the esophagus, or the swallowing tube as it's sometimes known as, into the stomach, and then it goes into the small bowel. You have 20 feet of small intestine in you. The uppermost portion is the duodenum, the middle portion is the jejunum, and the lower portion is the ileum. Now, the ileum is about an inch-and-a-half or so in diameter and width. And that connects into the area of the large intestine, which is called the cecum. This area here is the cecum. So the ileum and the cecum come in together. And as you move your bowels, the stool goes through there, and it exits through the rectum.

Dr. Lichtenstein: Ulcerative colitis can inflame the rectum, proctitis we call that. It can inflame the left side of the colon. We call this left-sided colitis. You might see something called distal colitis. Distal means the lower portion of the colon. And then there's pancolitis, pan meaning the entire colon, colitis meaning inflammation. The small bowel is not involved.

Now, when you present with disease of ulcerative colitis directly, what is the likelihood you're going to have severe disease? [The likelihood is] very low. Most people have moderate activity or so. About three-quarters of individuals are going to have moderate activity, and mild activity is about one in five. So the chance of having severe activity initially is pretty low, which is good.

The symptoms of colitis depend on the extent of the inflammation; is it the proctitis, the left-sided colitis or the pancolitis? How bad [is] the inflammation? And the typical symptoms you might expect are bleeding from the rectum, an urgency to evacuate, diarrhea, abdominal cramping from the stool just moving down in the bowel, and there may be symptoms outside the bowel. We call these extraintestinal, extra means outside, and intestinal means the bowel. Joint pain or swelling [are also possible symptoms]. Eye inflammation [can be a symptom], so I recommend people to see an ophthalmologist to examine the eyes once every year or couple years on a routine basis. Skin lesions [can also occur].

When we have people that come to see us who have ulcerative colitis, we tell them there can be complications that come about with the disease.

There can be cancer. There can be bleeding with colitis. There can be perforation [of the bowel wall], which is pretty uncommon.

stricture formation, narrowing of the bowel, [is another complication of ulcerative colitis]. When you have [stricture formation], you always have to worry, “Is there a growth [polyp or cancer] there?”