Dr. Lichtenstein: So research in IBD, where are we heading? There are several things: Mesalamine, Asacol, there's an 800-milligram mesalamine tablet that has now undergone two large trials and works. So I suspect that will be on the market shortly. So instead of the 400 milligrams we currently have, the 800 milligrams is going to be coming, so it will be [fewer] pills, and it's easier to take.

Targeted antibiotics, Xifaxan, rifaximin: This is now on the market. It's FDA-approved for travelers' diarrhea. It has less than 4 percent absorbed, 96 percent is in the intestinal lining. It's been used in Europe for 17 years. It's got substantial use. We've used it, and we're presenting this at our national meeting for treatment of pouchitis, for treatment of Crohn's, and for treatment of bacterial overgrowth. It is effective.

Biologics: Tysabri, natalizumab, this has been put on hold just recently because of a side effect. But this is a targeted antibody like Remicade, infliximab. It's given intravenously, but it works on the uptake of the white cells into the veins. [Medical editor's note: It was first approved for multiple sclerosis and is still being studied in Crohn’s disease.]

Humira, made by Abbott, [also called] adalimumab: This is on the market. It's FDA-approved only for rheumatoid arthritis. There are preliminary findings that it looks very good for Crohn’s disease so far. But there's a large trial. It's not FDA-approved, and it's costly, so you would want to get approval from the insurance companies before you use it. We've used this on numerous people - probably about 50 people to date I've used it on for treatment of Crohn's. And it does work. And it's in people mostly that have had side effects from Remicade [infliximab], or they've lost the effectiveness of Remicade over time. So they get a rash or something where they shouldn't take it again.

And then Leukine [sargramostim] is on the market. It's used to treat people that have low white cell counts related to chemotherapy. And there are trials ongoing now, but we've also used that for people with Crohn’s disease, and it looks very promising today. So I expect these will be on the market shortly [pending FDA approval for Crohn’s].

The research for the 5-ASA, the 800 milligram tablet, we spoke about. The Phase III trials have been completed. They've been presented. They've been submitted now for publication. The FDA is looking at this and I believe will approve this.

The antibiotic Xifaxan, it's being studied for use in inflammatory bowel disease for postoperative recurrence, for preventing the recurrence in Crohn's. I know there will be a large study. I wrote the protocol for this on a national level, so we'll look at this since it's very well-tolerated, there are virtually no side effects with this antibiotic, and there's no resistance, which is the important thing clinically.

Tysabri, we talked about. It's the first in - called the small adhesion molecules or SAM for short, small little molecules that stop the white cells from attaching to the veins, adhesion molecules. The trials are currently on hold.

And then Humira, this is given in the skin so it can be taken at home, subcutaneously, under the skin like insulin is given, and it's very similar to Remicade. It inhibits TNF in the same mechanism we look at. [Medical editor's note: TNF causes inflammation and is at the heart of several inflammatory diseases.] And the FDA has approved this for rheumatoid arthritis. Phase III trials [are being done in Crohn’s disease], and we expect that in 2006 this will be approved. Side effects are relatively few: Infection, headache, rash and injection site pain are the most common.

And then Leukine [is in] Phase III clinical trials. The FDA has approved this for oncology. It's on the market. It's given for transplant indications, and it's relatively safe medication, which is terrific.

In genetic research, there's a lot going on as well. There are now several genes being looked at for ulcerative colitis and for Crohn's. The multi-drug resistant gene has been the most common or the most recent one added for ulcerative colitis. We're likely to identify multiple different genes that are abnormal, and these may characterize, in other words identify, what a disease state a person may have, and that's what we're looking for down the line. To say, "You'll have ulcerative colitis limited to the rectum. It's not going to progress, and you likely won't need surgery." That's what we'd love to have, to take a blood test to do that in the future.

The manipulation of the genes, we've done a lot of in our institution as have many other places to try to change the genes that are abnormal. Can we go back and make them normal?

And then identify bacteria-causing disease as well, this is a big area. Normal bacteria produced in an abnormal immune response, the body's white cells are too revved up, they go into the bowel, can we stop that? So there are interactions between the bacteria and the epithelium, the inner lining of the bowel, and then also the immune system, mistaking itself, gene micro-organism interaction, in other words, bacteria and the genes working together in concert.

The research and surgery: Ileoanal pouches, prevention of pouchitis, minimally invasive surgery, now laparoscopic surgery, doing pouch surgery at many institutions and also Crohn's surgery and recurrence of the Crohn’s disease prevention is something undergoing trials.

Dr. Lichtenstein: How can you help to be involved in this? There are several things you can do. Volunteer to participate in clinical trials if you qualify and it's appropriate, under the supervision of a physician that's treating you to ask them first. And clinical trials are how we learn with new medications. This is the only way. Animal models don't really help us as much as we'd like in Crohn’s disease. So this is something that's important directly.

Dr. Lichtenstein: Dr. Gaspari, [can you] comment on increasing liver counts with using 6-MP? How high in counts can we go before [there is] a big concern with liver problems in the future?

Dr. Gaspari: It's not unusual to sometimes get a little bump in the transaminases [liver enzymes]. Whenever we see those though in someone, especially if we've recently initiated therapy with 6-MP or azathioprine, that's a reason to be vigilant about where those numbers go. If those numbers would continue to rise, it might be a cause for concern. It may indicate that that individual is not a candidate to use those medications.

Sometimes we'll see a slight bump in the numbers to less than two or three times normal that, with time, will come right back to normal. But it is something that would raise concern and would require a careful monitoring.

Audience member: If you had someone in whom you started a 6-MP or Imuran [azathioprine] and their liver chemistries did increase - if you did the 6-TG and the 6-MP metabolites and the 6-MP level was within normal range not in the hepatotoxic range - would you be comfortable with that, that that was not related to the immunomodulators?

Dr. Lichtenstein: There are some blood tests that can be gotten through a laboratory called Prometheus Laboratories, and that's a lab in California where you measure a blood sample, and you look at some blood material to look for two different things. One is called 6-TG, which is the initials TG, which is short for thioguanine, and the other is 6-MMP, methyl mercaptopurine. The thought is that the higher level of TG, 6-TG, the more likely it is that the person will respond to the medicine, azathioprine, 6-MP, Azasan [azathioprine], Imuran, those are the medicines we're talking about. 6-MMP is thought to be associated with liver damage. So the liver test being abnormal, this may measure that.

The problem is it's not a very good test, 6-MMP, and you can have several different scenarios, in other words, possibilities. You have a high 6-MMP level in the blood if someone does order that, and the liver tests are normal. Just keep following the liver test. Don't change anything. There's no recommendation to stop the Imuran, 6-MP directly or the Azasan. Stay on that.

If, however, the liver tests are abnormal and they're two to three times abnormal, then it often indicates that the dose that the individual is on who has those abnormal liver tests is too high for that person, so they might try lowering the dose of the medicine somewhat, and then they'll usually go away.

And then the other scenario is, both correlate very well directly, the 6-MMP and the liver test being done so they go right hand in hand. But, in general, we don't measure that to see directly if it's caused by something else because there can be other medicines that cause liver test abnormalities in other things. So one might have viral hepatitis, hepatitis A from eating shellfish. So there are several possibilities for that. I don't rely on those personally.

Audience member: Could you talk a bit more about systemic difficulties, the eyes, the skin, what other things that might be important for individuals as patients or family members to look out for?

Dr. Sigmon: The eye manifestations are pretty rare, but when they occur they're pretty dramatic. You can have what looks like a severe case of conjunctivitis where the lining of the eye - the white of the eye - is very, very red. As Dr. Lichtenstein mentioned earlier with steroids, you have the risk of subcaps or cataracts, and that's something to be on the lookout for.

There is probably a 5 to 7 percent instance of joint problems for patients with inflammatory bowel disease, and, in fact, one of the very first patients who is now a 27-year-old policeman in Rock Hill that I saw when he was 13 years old presented with arthritic problems and then turned out to have Crohn’s disease. So you have to watch out for arthritic problems.

As Steve mentioned earlier, the skin manifestations [that] are the most dramatic [are] pyoderma. Probably one of the most painful is the erythema nodosum. Then there's something called granuloma annulare, which is sort of a red circular area on the skin.

There [are] some patients who have pulmonary or lung problems sometimes associated with the medications. I've had patients who've had hypersensitivity or lung sensitivity to mesalamine products and developed difficulties with their breathing on those medications.

And then as he mentioned, there [are] the bone thinning problems, the osteoporosis with the early fractures that are again extraintestinal manifestations. I think that covers most of them.

Dr. Sigmon: Kidney stones, especially if they have terminal ileal disease they can get oxalate stones because there is a problem with the absorption of calcium, and they can develop calcium oxalate stones. Sometimes you have to put those patients on low-dose hydrochlorothiazide, which is a diuretic to help them to get rid of some of that excess calcium.

Dr. Lichtenstein: So now let's change gears a little. We have someone in the audience who's written, “I'm age 46. I've been on Remicade [infliximab] a year. I have fistulas in my small bowel. I'm doing great. How long can I expect to be on Remicade? Is it years, is it very easy to stay on this long term, and should I expect to be on this the rest of my life? And once I go off, in other words, what's my therapy treatment then if I were to go off this?”

How long [is treatment], and are there other things that work for fistulas besides Remicade?

Dr. Gaspari: I think the answer to that question may change with many years more of experience with Remicade, but I would say that with our current state of knowledge the answer to that question would be that Remicade is your maintenance drug. It's working well for a very difficult problem to treat traditionally in Crohn's disease, which is fistula disease. There aren't a whole lot of things that work well for fistulas disease, and I would certainly say that Remicade works the best for fistulas disease of any of the things that we have, at least [for] conventional therapy it works the best. So I think that the way that I approach that problem is that this is an individual who had a really severe problem with Crohn's disease, is doing well on Remicade and should continue on Remicade to keep that problem at bay.

There is kind of a secondary issue, and that has to do with problems that we occasionally see in folks that have been treated with Remicade in the past who have gone for relatively long periods of time, six months or a year, without being treated and then get retreated with Remicade. And it's that group of individuals that we see a side effect - in a percentage of them - called a delayed hypersensitivity reaction, which can be very uncomfortable. It's what we used to call a serum sickness reaction, and typically it's associated with fever and joint pain and rashes and can make someone feel really lousy.

So it's part of the reason that in someone who has been treated successfully with Remicade who is on a maintenance program and doing well that we're reluctant to stop treatment and see how things go. fistulas disease is one of those things that we can often count on seeing it again even when things are going right. So if you're doing well, I think the answer is that you stay on Remicade.

Dr. Sigmon: I agree with that. The only thing I would add is that there - I think it was a retrospective study at Mount Sinai, Janet [Dr. Present] was in that group looked at use of Remicade in patients who were on 6-MP and Imuran-type medications and found that if they were on those immune modulator therapies and then got Remicade - the effect was a little longer than if they weren't on that. So I try to get our patients on 6-MP or Imuran if they have fistulas disease because before we had Remicade there were actually some studies to show that that might benefit fistulas disease. Although it takes a long time for that to get better, a lot longer than it would with Remicade, but there may be some additive effect of the two medications or the two treatments, the Remicade and the immunomodulator medication, so I'm not sure what your experience is with that.

Dr. Lichtenstein: So I'll just summarize some of the things that he said. I concur with a lot that he said. We have a lot of medicines to treat fistulas. Surgery is needed, about 80 percent of people that have fistulas at some point are going to need surgery. The important thing is to go to someone who knows the medicines and how to use them. Antibiotics might be used at first. Cipro [ciprofloxacin] and Flagyl [metronidazole] being the classic ones that are available. If that doesn't respond or it recurs, you might use infliximab, Remicade, an immunomodulator, 6-MP, azathioprine, Imuran, Azasan all being the same. Methotrexate has also been shown in some very small studies. Dr. Present was one who showed us that it does work in about a third of the people directly. And he was also one of the first to show us that 6-mercaptopurine was effective in treating fistulas.

So we have a medical armamentarium, a group of medicines that are available that we can combat and treat fistulas with. I think they're debilitating. They're problematic, and seeing people that have treated people with Crohn's before and have experience is very important. As you can see, knowing this important information is critical.

Simple question: Is there a progression from ulcerative colitis to Crohn's? Someone probably was told they have an ulcerative colitis initially and then came out, and then they had Crohn’s disease is my guess.

Dr. Sigmon: I've actually seen situations where we thought the patient had Crohn's disease by the distribution and the biopsies, and then years later or at some point in the future it looked like they had ulcerative colitis. And I think more often we see the other side of that where patients were thought to have ulcerative colitis and they have their surgery, have a colectomy and then the J-Pouch surgery that was described. And they developed fistula in the J-Pouch, and it turns out that now they have Crohn's disease. And both of these are immune-mediated diseases.

And granted, there are some differences, but I suspect that years from now we're not going to be talking about two entities - Crohn's disease and ulcerative colitis - but we're going to be talking about several where there is some indeterminate issue there or situation where there [are] similarities between those. And there'll probably be several disease processes that we are talking about in the future because I think they overlap quite a bit.

Dr. Lichtenstein: [There are] two questions I want to interject now. I had mentioned maintaining remission. Is that necessary to really have total remission to continue the agents, the mesalamine, the 5-ASA medicines?

And also when I say remission, is that a certain amount of time, a certain number of years, is it based on certain symptoms, what can we tell? I guess that's an important area to understand in the context of everything, what is remission?

Dr. Gaspari: Well, there [are] different ways of defining remission. We have a formal way of defining remissions in clinical studies. For example, in Crohn's disease, there's something that is referred to as the Crohn's disease activity index, and it's a score that is generated by combining a number of different things including symptoms, primarily symptoms, the frequency of bowel movements, the number of bowel movements a day, the presence of abdominal pain, any of the extraintestinal manifestations. So we put those numbers together. Certain numbers are given different weights as far as its importance in the score, and the number that you total up gives you the Crohn’s disease activity index. Well, when that activity index is less than 150, that person is in remission by definition.

Well, most doctors in their office are not scribbling down numbers and figuring this out. We find out whether someone is in remission by asking them how they're doing and then by their assessment as to their bowel movements and abdominal pain etc. So it's a less formal way of defining remission.

It really doesn't have much to do with time, unlike you would think of a cancer remission for example. You're six months out or a year out from the diagnosis, and your disease is in remission. For example, in some patients treated with Remicade, in some patients treated with steroids, remission can occur within weeks.

When you talk about maintaining that remission, you can also talk about maintaining improvement. So you don't need to completely turn off the disease in order to talk about maintenance therapy. For example, in someone that responds to steroids, well, we don't want to use the steroids for a longer period of time that we have absolutely have to get that individual feeling better. They may have some residual symptoms, their stool frequency may be more frequent than they would want. Yet we're happy with the improvement, and the maintenance therapy then is aimed at continuing that improvement.

Dr. Lichtenstein: Is it common to take medicines together? I talked about Imuran, Azasan, 6-MP, the immunomodulators and mesalamine such as Colazal and Imuran. Is that something that can be done routinely and if you say yes, why, and if no, why not?

Dr. Sigmon: It's pretty common to have patients on several different medications, and we're getting better about doing that than we used to. The rheumatologists do that quite frequently and what we're doing is targeting the various players involved in the immune response. And with Colazal or Asacol or Pentasa or Dipentum or Azulfidine - which are the mesalamine-type medications that have the five aminosalicylic acid active component - we're targeting a particular part of the immune system and trying to tone it down.

And with the immunomodulators - Azasan, azathioprine, Imuran, Purinethol, the 6-MP - we're targeting a different part of the immune system, trying in total to sort of turn that off in some respects so that the body in essence stops reacting against itself. And so it's very common to use those medications in concert, and we follow different things to monitor that therapy, the white blood cell count and the red blood cell count with the immunomodulators, and with Asacol and Pentasa. And we usually check the kidney function test just to make sure that that's in order. Even though it's very unusual to have kidney problems, that is a potential side effect, and so it's not unusual to use those medications together.

Dr. Lichtenstein: Another question: How serious is mild bleeding in a person with ulcerative colitis that lasts two to three months?

So I'm guessing they're not having any significantly active symptoms. They have known ulcerative colitis, is this something that needs to be evaluated? I can think of several scenarios where they've had recent colonoscopies, they haven't. You might want to just touch on this as to what colonoscopy might be helpful for.

Dr. Sigmon: The goal, as some of the last slides indicated, was to improve the symptoms, and one of the symptoms of patients with ulcerative colitis as well as Crohn's colitis is blood in the stool. That can be alarming no matter what, but we would like to have all things be perfect, there be no blood in the stool. But if there's a small amount there, we don't want to just focus on that one symptom. We want to know about the frequency of the bowel movements, the urgency or the getting up at night to have a bowel movement, are they gaining weight in reference to children, [are] there fever, do they feel good? And if all things being equal and the only thing that they're exhibiting is blood in the stool, and the hemoglobin or the red blood count is normal, and they've had a recent examination of their colon to know that it's not something else, then I don't get too worried about some blood in the stool. We'd like to have it where there was none, but that sometimes isn't that realistic.

Dr. Gaspari: One of the things that we'll often do in a patient like that, I think as Dr. Sigmon said, the one thing that we want to make sure of is that we've ruled out other reasons for the blood in the stool. But assuming that that's been done, the bleeding is related to inflammation the use of a rectally administered medication such as Canasa [mesalamine], suppositories or Rowasa [mesalamine] enemas where we're getting concentrated medication directly to the distal rectum, the end of the rectum, which is typically where that blood comes from, is often helpful. Many times individuals don't like rectally administered medication, but this is one of those situations where it may take care of a relatively minor problem very, very specifically.

Dr. Lichtenstein: Let's go over foods now. A lot of people have questions on foods. So let's start first with favorable foods. Are there certain foods that might be advisable? And that's with the caveat of, remember, not everyone is going to be affected and some people may be affected sometimes but not all the time.

Are there any things that we might advocate, we might suggest would be appropriate for people, foods that are good and less irritating or problematic, Dr. Gaspari?

Dr. Gaspari: There are always questions about diet, and, unfortunately, the amount of information is almost counter to the amount of interest in dietary information. The standard line is that there is no inflammatory bowel disease diet, so there are no specific food selections that are going to turn off - or for that matter turn on - your inflammatory bowel disease. I think the problem with nutrition in inflammatory bowel disease is simply the problem of nutrition that everyone has to deal with. You want to make sure that your diet is a healthy one.

You can have problems that are related to diet and are related to specific diseases that don't really have anything to do per se with inflammatory bowel disease. Celiac disease is a condition that we are now appreciating more often that was something that was under the radar for many years. There are now specific blood tests, and we're more inclined to look for that in folks that come in to us, for example, with irritable bowel type symptoms. You can have irritable bowel syndrome and inflammatory bowel disease, and you can also have celiac disease and inflammatory bowel disease. So that might be a situation where we look for that disease, and if that is diagnosed then some very specific diet recommendations will be helpful at controlling symptoms.

The same could be said of lactose intolerance. It tends to be more of a bothersome problem than a disease per se, but it certainly could contribute to symptoms.

irritable bowel syndrome is again another one of these things that can overlap. It's a very common condition, so folks with inflammatory bowel disease can have irritable bowel symptoms as well, and that's a condition where diet modification may be helpful at controlling symptoms. But it doesn't imply that you're really affecting the underlying inflammation that's part of inflammatory bowel disease.

There are other situations in inflammatory bowel disease patients where diet modification may be helpful. And an example of that would be a patient with Crohn's disease who has significant stricturing of the small bowel where mechanical issues are important. In other words, you want to avoid roughage because it's going to plug that smaller hole and end up causing obstruction in that individual. A lot of times in patients with active ulcerative colitis, we avoid roughage just because the colon may tend to have a tougher time handling roughage in the face of active disease.

Dr. Lichtenstein: How about multivitamin supplements, what do you tell people that walk into the office, Dr. Sigmon? Should everyone take a multivitamin who has Crohn's or ulcerative colitis? Many times, they don't tolerate them. There may be some iron or other things that may be difficult to take.

Dr. Sigmon: I don't recommend the iron supplements unless someone is anemic. And if they're anemic, then I think they're beneficial, and there are many of them out there now that are very tolerable to the GI tract. I am a proponent of Centrum A to Z because it's got zinc in it, and the zinc is really important in patients who are having diarrhea because you can lose a significant amount of zinc in that way. And zinc is helpful in promoting the immune system, and I'm sure you're familiar with the zinc lozenges that are pretty popular during the flu season in people that have colds and sore throats, and that's where the zinc lozenges play a role in that respect. But for a long time, I've been a proponent of using zinc supplements, and that's an easy way to get them is through Centrum A to Z. There are probably other multivitamins, but that's just the one that comes to mind.

There are also prescription vitamins that have zinc, and there's one that I like called Glutofac ZX, and it's got a good amount of zinc as well as some vitamin B complexes.

If you're [on] Azulfidine [sulfasalazine], then your risk of folic acid deficiency goes up, and we always put people on folic acid. And if you can get a multivitamin that has folic acid in it, then that's a double whammy that helps because there are B vitamins and B complexes in that.

I like to tell people about aloe vera gel caps. I can't stand aloe vera liquid. It's nasty, but the gel caps are pretty good. And aloe vera is a natural inhibitor of some of I think Interleukin 6. We actually did a study years ago using aloe vera in patients with ulcerative colitis, and it's not harmful.

And then lastly, I like grape seed extract, which is an antioxidant, and I think that that's beneficial in inflammatory responses.

Now, there's no data on the aloe vera that I can recall or the grape seed extract, but knowing what effects they have in terms of anti-inflammatory effects, I think they're beneficial.

One thing to add about the diet is - the pediatrician part of me comes out - if you're having problems with diarrhea, you want to avoid the fruits that begin with the letter P, particularly prunes and pears, because they have a lot of sorbitol in them. And, as you know, sorbitol can cause you to have diarrhea. And we try to concentrate on the fruits like apples and bananas that have pectin in them, which is in Kaopectate, which helps you when you have diarrhea. But as Dr. Gaspari said, there is no magic inflammatory bowel disease diet. It's an individual thing.

Dr. Lichtenstein: There's actually been just recently a controlled trial, [and] it's more effective than a placebo, aloe, for ulcerative colitis.

So is the medical community far from finding a cure for ulcerative colitis?

Dr. Gaspari: I think that we're still a ways from finding a cure. The one thing that I think is the brightest thing on the horizon is the genetic research because when you get down to a genetic level then you've at least got a chance of figuring out a specific cause of a disease. Now,, in inflammatory bowel disease it's not going to be one cause, it's going to be a variety of things. And in fact genetic research is probably going to help us to separate these diseases into different categories as Dr. Sigmon alluded to earlier.

I think we're a ways away from a cure. I hope I don't sound too pessimistic, but I think these diseases are going to be with us for a while yet.

Dr. Lichtenstein: Is Crohn's curable?

I'll say as of now the answer is no. Is a question people have asked, “I've heard that Remicade can cause death, is this so?”

Well, this is something that anyone could die of for many reasons. The big concern is long-term use of steroids, and we've just done a large study with what is called the TREAT Registry funded through Centocor that looks directly to see. And it's more the steroids, the prednisone, long-term that's a problem. There was no higher rate in people on Remicade versus people taking other medicines for general treatment. So that's something.

Diabetes: Does it affect Crohn's and ulcerative colitis? [Are there] any special considerations for someone with diabetes and Crohn's or ulcerative colitis?

Dr. Sigmon: I think my concern about that would be that if you have a patient who's got diabetes, you have to be very careful with putting them on steroids because that could aggravate their diabetes pretty significantly, raise their blood sugar, throw off their ability to regulate their insulin.

And then sometimes patients with diabetes have problems with overgrowth of bacteria in their small intestine because the diabetes affects the nerves that control a function of their small bowel. And when that slows down, then that can allow bacteria to overgrow in the small bowel and contribute to diarrhea and aggravate their inflammatory bowel disease, and you may not know which problem is more active.

In that situation, the Xifaxan [a newer antibiotic], which we've been using more regularly now, might be beneficial because it would focus on the problem of the bacterial overgrowth. And in terms of ideologies or cause and effect, I don't think there's any increased instance of inflammatory bowel disease in patients with diabetes.

Dr. Lichtenstein: Okay, [we have] two more questions, and then we'll open up.

Individuals that have Crohn's can't get into remission, are on prednisone. They have disease that is dependent on prednisone. If you would, whether it's Crohn's or ulcerative colitis, what are the potential medicines that we have for them that can be considered?

Dr. Gaspari: Well, I think we have several. The immunomodulators would be one [class] of the drugs that we would consider in someone that seemed to have problems getting free of steroids. Because that to me is one of the goals of treating inflammatory bowel disease - is to be able to treat patients and get them under control but get them off steroids under control. And I think the vast majority of patients we're able to do that for.

Remicade is another drug that fits the bill as a steroid-sparing drug and as a good maintenance drug.

Sometimes the 5-ASA drugs are given short shrift because they are felt to be lightweight drugs. Well, I think in Crohn's disease and someone with severe Crohn's disease that is true most of the time. Although sometimes it's amazing how well a patient with Crohn's disease will respond to 5-ASA medications. I'll tell you that 5-ASA medications are not approved by the FDA to treat Crohn's disease, but it's probably one of the most common drugs that we use despite that fact.

In ulcerative colitis, sometimes we see that the problem is that the dosage of the 5-ASA drugs is not sufficient. I think that used to be more of a problem than it is now. We all have gotten the message that 5-ASA drugs often need to be used at higher dosage than we may have traditionally used in the past.

And then the other thing I'll mention is that it's very important to look at factors other than drug treatment for managing these conditions. And two examples are patients with Crohn's disease that continue to smoke. It's a big problem and I harp on - I'm kind of relentless on my Crohn's disease patients that continue to smoke. It's bad news, and it definitely is a contributing factor.

The other issue is the non-steroidal anti-inflammatory drugs in patients with inflammatory bowel disease. Sometimes people haven't heard that those drugs can cause problems, and they need to be aware of that and if that's one of the factors that they need to be off those medications.

Dr. Lichtenstein: Someone has ulcerative colitis or Crohn’s disease, how do they know if they have irritable bowel syndrome superimposed? What are the things that we can help establish? Are there certain tests they can do? Is there finding? How is that determined? And what can they do?

Dr. Sigmon: That's a good question. That's a tough one. irritable bowel syndrome is a symptom-based diagnosis. In other words, there are no tests to diagnose irritable bowel syndrome. There are a set of criteria that were developed by a group of people that were [called the] Rome II criteria. And that is a patient who has abdominal pain or discomfort for 12 weeks or more in the preceding 12 months, a patient who has alternating bowel habits, diarrhea and/or constipation. They talk about loose bowel movements, or they get into the description of the type of bowel movement, and then the patient with abdominal pain that's usually relieved after a bowel movement. People have urgency and bloating.

But the three things that you hear about a lot in patients with irritable bowel are abdominal pain, bloating and then an alteration of the bowel habits.

It's very unusual for a patient with inflammatory bowel disease to be constipated. It's not impossible by any means, but it's just unusual. But patients with inflammatory bowel disease who are having abdominal pain and diarrhea without blood in their stool, without fever, without an elevation of their white blood cell count or platelet count, with a normal hemoglobin, or red blood cell count, are more likely having a flare of their irritable bowel syndrome than a flare of their inflammatory bowel disease.

So there's no simple approach or answer. Again, it's an individual thing, and you have to measure a lot of different things to determine whether it's related to inflammatory bowel disease or irritable bowel syndrome.

Dr. Gaspari: Symptoms that are transient and meal-dependent are more likely to be irritable bowel syndrome. You eat a pizza with everything on it, well, that didn't cause a flare of your Crohn's disease or ulcerative colitis. It's more likely that if you get terrible symptoms that last for hours or a couple of days and then resolve, that may be more of the problem with irritable bowel syndrome than inflammatory bowel disease.

Dr. Sigmon: And the other thing is it's very unusual for irritable bowel syndrome to wake you up in the middle of the night to go to the bedroom to move your bowels. So that's usually an inflammatory process.