Dr. Korzenik: Surgery in IBD is an important area that we sometimes think of it as a sort of failure. Well, [when] someone is doing terribly, we’ll just have to send them to surgery. Sometimes surgery can be the best available therapy and really can be a wonderful thing.

In ulcerative colitis, surgery is curative [because the entire colon is removed]. It’s not a cure that we would want if we had some other therapy, but it is a good option. We’re not talking about for most people an ileostomy, but for some people the ileum is brought out to the skin [ileostomy], and that can be the surgery in itself. The other option is a J pouch. [Medical editor's note: Instead of bringing the ileum out to the skin, the ileum is reshaped into a pouch in the form of a J, which acts as a rectum, so there’s no need to where an external appliance as in an ileostomy.] When they’ve done studies after people have had colectomies [removal of the colon], 95 percent of people say that their quality of life is vastly improved. And I would say the comment that I get most from patients after this is, “I probably should have done this two years ago.” So it often can be a very good operation with very good results, typically, after a J pouch. So J pouch is where the last part of the small bowel is brought down and turned into a J, and then the walls in between are sort of opened up. And then the bottom of it, the bottom of the J, the curve of the J, is attached to the anus, and then you have a pouch there that functions as a new rectum. It’s not the same as having your colon because the colon works to absorb a lot of fluid, but you’ll typically, with this, have perhaps about six sort of pudding-like stools in a day. Somebody might have as little as four. Somebody might have as much as eight to 10. But, typically, that’s where it is and you go to the restroom the normal way, and it can be a very good result.

[For] Crohn’s, on the other hand, surgery is not a cure. There is a high rate of recurrence. Typically, it’s about 15 percent of people who have had a resection of their small bowel will have recurrence each year clinically. But if we look in with a scope, it’s as high as 80 percent will have some evidence, or even higher, will have some evidence of disease at six months or a year after surgery, which will often do that to try and get that early and try to be more aggressive if disease seems to be coming back faster. If somebody has colitis and has an ileostomy for Crohn’s, disease recurrence is much less. And for the majority of people that might even be the end of it for their Crohn’s, and having an ostomy can be very good and effective.

Why would we go to surgery in ulcerative colitis? Certainly, if someone is having a refractory disease, and is just really severe, or it’s just been going on for a bad flare, or somebody has what’s called toxic megacolon, [when the] colon sort of balloons up and can be very sick. If somebody has some other acute complication of perforation, bad bleeds, something like that. Or if there are just chronic symptoms which aren’t necessarily as awful as a day-to-day thing, but it’s just been going on too long. It’s not allowing the person to get on with their lives, then that can be very good. Or different medication side effects: Typically, if someone is steroid-dependent and not responding to other medications, that can be a reason.

One of the big [reasons to perform surgery] is dysplasia or cancer. Dysplasia is something that is sort of a forerunner of cancer. Dysplasia is a subtle change in the cell architecture or the way the cells look under the microscope that can suggest that there’s cancer either elsewhere or that it is leading to cancer. And so that in itself, even without identifying a frank cancer, that in itself would be a reason to have the colon out. And not just that segment [would need to be removed], but it means there’s probably cancer elsewhere in the colon, so the whole colon should come out. If somebody just has a little bit, say just the left side of their colon is diseased, we don’t just take out that left side because the likelihood of recurrence is so great that we would say it’s important to take the whole colon out.

For Crohn’s, as we talked about, you can get stricturing. It can narrow down, and that can be nearly obstructing or obstruct somebody, and that’s an indication for surgery. For complex fistulas that are causing all sorts of troubles, for perianal abscesses, all these things are important [reasons for surgery]. Or if there’s local and unresponsive disease that’s not responding to any medication, that can be a cause to get out in itself [i.e., get out that piece of intestine that is unresponsive].

Dr. Korzenik: I don’t want you to have the impression that if you have chronic inflammation, with Crohn’s, with ulcerative colitis, that [cancer] is hanging over your head, that it is inevitable - it’s not. It’s just something you need to know about, so you can manage. It does happen at a much higher rate than the background population and typically can happen at a lower age, but it doesn’t mean that it’s inevitable. It is important to recognize that it occurs in Crohn’s, colitis, as well as in ulcerative colitis. And if you’re someone with primary sclerosing cholangitis, particularly liver disease, it seems that that’s an even increased risk than the background population. Recently, it’s been identified that if the disease is under very good control so that there is not inflammation that reduces the risk. It may seem obvious, but it took us a while to be able to prove that and to feel confident in saying that.

Now what can we do to try to reduce the risk of colon cancer in inflammatory bowel disease? The 5-ASA agents - the Asacol, the Colazal, Pentasa - all those things have been suggested to decrease the risk of colon cancer. So it’s one more reason to take them. The effect is mild, but it’s been shown in a number of studies. Not all studies have shown that, but it does look like they can help decrease the rate of colon cancer. Some of us do put our patients on folic acid. There’s some evidence that folic acid may reduce the risk of colon cancer as well at a higher dose than in a typical multivitamin, which is 400 microgram. We’ll often give 1 milligram, and regular colonoscopies [can help].

Now in a colonoscopy for someone who doesn’t have ulcerative colitis or Crohn’s, what we’re looking for are polyps, the little grapes that are sort of hanging down that we can pluck off and prevent them from going on to colon cancer. Unfortunately, in ulcerative colitis and Crohn’s, the cancers aren’t sort of forewarned by a polyp, and they can happen in just flat intestines. So what that means is when your doctor’s going in, he or she is going to take at least 33, 35 biopsies to sample the entire lining to be able to see if there are any of these changes that might indicate this dysplasia and a problem. Now, if there is dysplasia identified, that would be an indication for having the colon removed.

Dr. Korzenik: Where are we heading with research? There are some things that are moving forward in terms of the basic things, small improvements. Asacol [mesalamine] will soon be coming out with an 800-milligram tablet, so reducing the number of tablets you need to take on a daily basis. There are new antibiotics that are being looked at, such as Xifaxan or rifaxamin, which has been approved for traveler’s diarrhea but is being looked at with exciting promise for Crohn’s disease and possibly pouchitis.

There are a number of what we call biologics. There’s one called Tysabri [natalizumab], which is currently under a cloud, and we’re not sure whether it’s going to come back [on the market] because of some side effects that have been identified. Mostly, it’s a drug that looked extremely effective in multiple sclerosis, had been fast-tracked by the FDA because it was so effective, and then some very unfortunate side effects were noted in just three patients so far. And so that’s being investigated further and seeing whether it is a broader problem. There has been recently a little bit of a swing toward thinking it is going to come back, but it’s not clear.

Humira [adalimumab] is very much like Remicade [infliximab], but unlike Remicade it doesn’t have the mouse portion. So Remicade, 25 percent of that molecule comes from a mouse, and that’s where your body can recognize it is foreign and make an antibody to it and reduce its effects from this. Humira is something that’s been approved for rheumatoid arthritis [and] is not from a mouse protein, so your body won’t reject it. It’s not yet approved for Crohn’s, but the preliminary studies look extremely promising and look like it should be as effective. It’s given as an injection, not as an infusion, and in people who have responded to Remicade but lost that response this looks extremely effective at reestablishing that response. You need to be on a higher dose than rheumatoid arthritis, but it’s a very promising thing.

And Leukine [sargramostim] is something that I’ve been involved in developing, and I’ll talk about it just for a brief little second just to give you an insight into it. And it may be a little confusing in that it’s a very different approach. So as you’ve gotten the sense of most of these medications here are looking to try to suppress the inflammation, control the inflammation in Crohn’s. A colleague and I are proposing that Crohn’s may be a little different disease, at least in some people, and it may not be too much inflammation. It may actually be too little inflammation. If you have a cut on your leg, bacteria get in there within seconds to minutes and you have a rapid response team of cells that come in there to clean it up, heal it up, and allow it to heal without any problems. What we’re saying is that in some Crohn’s patients for a variety of problems, that rapid response team is defective, that it is not able to rush in there, clean up the bacteria and take care of the problem. So other cells come in, and they’re not equipped in the same way to handle it. So they’re sort of spinning their wheels, creating all this inflammation. And so what we’re saying is that, yes, suppressing that secondary inflammation can be helpful in some people, but perhaps, in some people, rather than suppressing that side if we just boost up that rapid response team that might get a very good benefit. So [those are] some studies we’ve been doing that have worked out quite well, and you may be hearing about some studies that are coming that are going to be published this month showing a benefit of this approach. This medication [Leukine] has been around for a while but usually used, say, if you had chemotherapy, and you need to get your bone marrow rejuvenated - that can be quite effective for that. [Medical editor's note: It is not yet approved by the FDA for Crohn’s disease.]

So in terms of the new investigational tablets, it looks like it may be more effective at a higher dose than at the typical lower dose that has been used in Asacol. Adverse events were low and it’s really a way of allowing us to go up to a higher dose without taking more pills and maintaining or really improving efficacy.

Rifaxamin, as I mentioned, is a nonabsorbed antibiotic, so it doesn’t go into the rest of your tis sue. The likelihood of side effects is lower, and this is being looked at for use in inflammatory bowel disease. Tysabri, as I mentioned, currently the trials are on hold while we’re sorting out if the side effect that was seen is extremely rare or if this is going to be a broader problem. It’s a new class of medications in that what this does is it blocks the way that cells, that the inflammatory cells get into a site of inflammation. So there are various molecules that sort of grab the white cells that circulate in our blood and say this is where you’re needed. There’s a site of inflammation right here, and what this molecule does is it blocks that cell from grabbing a hold on to some of these white cells and reducing the risk. The unfortunate thing is it looks like it's effective, and it looked like it was extremely safe until this came along. So we’ll see what happens.

Humira, as I mentioned, protects. It seems to be quite similar to Remicade, and this has been approved for rheumatoid arthritis, and FDA approval [for Crohn’s] is expected in 2006. The side effects are quite similar to what’s seen with Remicade, and it’s good both in itself, but also particularly in those who have had adverse events to, or have good effect on, Remicade and then lost the effect.

And Leukine, as I mentioned, is a very different type of approach. There are currently a number of Phase III studies underway. Phase III are the studies that are done before something gets approved by the FDA.

So what else is going on other than therapy? One of the things that we’re very eager to do is identify genes. Because one of the things that is important in understanding how identifying a gene is it tells us a lot about what happens. What causes the disease? It’s a particularly exciting time [because not only has one gene been] identified, but there are a number of others that have been identified. And once we understand how the gene relates to developing the disease, then we have a very good clue in understanding how the disease should be treated appropriately.

We’re trying to also understand the bacteria better. You know, the gut is in some ways the final frontier. You have between 400 and 1,000 different types of bacteria in your gut, many of which we can’t [throw] out. Some are friends, some are foes. We want to understand that environment better, and we’re just developing new tools to be able to understand that better. And we also want to understand better how that bacteria interacts with the gene. And we now have ways. It used to be that we would measure a particular protein in your body and see if that’s elevated or not. We now have, with new technology, ways of identifying in one drop of blood looking at 10 or 20,000 proteins at the same time called microarrays. So, hopefully, that will give us a better insight into subtyping people and being able to say. And this is the best way of treating you. With that, we’re hoping that that will let us select subgroups and identify who is best treated with different medications.

With surgery, I think we’re making great advances in ileoanal pouches, and many centers now have a dramatically increased amount of experience and are doing them better. Some of them can be done now with laparoscopy and also looking at ways of preventing recurrence after surgery so people don’t have to go through that again.

Dr. Korzenik: Clinical trials: How does that, what does that mean to you, and how can you help? Volunteering in a clinical trial is something that is a very generous thing to do. Now, obviously, you’re getting involved in these trials because you want to get better. You’re having a problem, and you want to get better, or you want to help someone in your family or others, but it’s also helping the broader community of people with ulcerative colitis and Crohn’s. And so I encourage you all to get involved. It gives you access to some of the cutting-edge therapies that are available that are not broadly accessible yet.

Dr. Korzenik: In summary, ulcerative colitis and Crohn’s are chronic diseases, long-term medical therapy is needed. Quality of life can be impaired during flare-ups, but you shouldn’t say, “Well, I’m always going to have some problems. I’ve got Crohn’s. I’ve got colitis. This is just the way I’m going to be.” Sometimes people come into my office. I’ll say “How are you doing?” They’ll say, “Great.” I’ll say, “What’s going on, and how often are you going to the restroom.” “Oh, 12 times.” I’ll say, “What are you talking about then you’re great?” [They'll] say, “Well, I’ve got Crohn’s, what do you expect?” And we don’t want people to take that attitude. We want to get you back to how you were before, as close as possible as we can. And you shouldn’t accept a certain burden of disease because you have these labels.

Life expectancy should be the same as the general population, so it’s not as if you should somehow pack up your belongings and say goodbye to the world. This is something that we want to be able to keep as just a minor annoyance in your life. Staying on track with your therapy is very important. Working with your doctor [is important]. Working with your family is all very important. And surgery does have a role. There is a curative role in ulcerative colitis with its own troubles, and it can treat complications.

Dr. Korzenik: The question is, “I have a 13-year-old son diagnosed at 12. Can you speak to managing his nutritional needs?”

Dr. Leleiko : In general, it’s extraordinarily important to try to make a normal and a healthful diet. Now that means, in this situation, trying to have optimal disease control as well as to provide a normal, healthy, varied diet. Everything we know about nutrition and good nutrition, nutrition science, relates to obtaining food from a variety of different items rather than, suppose, to any one particular dominant food. So the question is about [how] a particular 13-year-old would relate to is that youngster’s growth normal? Has it been normal? Is there any evidence of delayed or failed growth? And those are questions that are addressed by your pediatrician or pediatric gastroenterologist when he or she looks at the growth chart and examines what the recent history has been. The general rule of thumb is at different times you encourage different things depending on how sick somebody is. But the focus, generally, is to try and maintain a normal life, which may mean for this particular youngster, if he’s very, very sick, he might do some unusual or extraordinary things. If he’s not terribly sick, it might be very important for him to have the same junk food that his friends are having when he is out with his friends. There is no such thing as a particularly bad food. There are terrible diets, and if we think in terms of what we know about nutrition and Crohn’s disease or ulcerative colitis, I’m not sure which. I think this was a youngster with Crohn’s disease. There are specific nutrient concerns that we might have for all teenagers. Someone with inflammatory bowels, especially, would be concerned about calcium intake. A lot of these kids, for one reason or another, are chased away from taking milk products. They are chased away from taking milk products, and then they’re going to most likely need a calcium supplement. So calcium is of concern. The other nutrient that they’re particularly concerned about at this stage would be iron if this is a young boy. I would be slightly less concerned that if this was a young girl who had already started her menses. But iron is a critical nutrient.

We have reasons to be concerned about a few other nutrients in the population, but I would not go overboard in terms of singling out any one nutrient for a particular child without specific indication. If one is concerned about it, a multivitamin is not a terrible thing. But you should avoid, here it says, high-potency or any of the specific supplements that have a large amount of any one nutrient. It is not a good idea to use them, and the best thing to do is to try and get the nutrition from a variety of foods in an otherwise healthful diet. I hope that answers the question.

Dr. Korzenik : Please explain how the Prometheus test is used in the prescription of 6-MP or Imuran [azathioprine].

Dr. Shah : In the old days, actually not so long ago, when we used a drug like 6-MP or azathioprine, we would monitor the blood counts, and we still do that. And we noticed that occasionally some patients would very quickly drop their blood counts, and we would always wonder why. And it turns out that we’ve been able to figure out some of the enzymes that are involved in metabolizing azathioprine or the trade name, Imuran, or another trade name Azasan, and also 6-MP.

So the body metabolizes azathioprine into 6-MP, and that gets metabolized further by an enzyme called TPMT. Now, we can actually measure either genetically whether you have two good copies of that enzyme or whether you have the right amount of the enzyme. And by doing so, we can predict kind of how you’re going to react to the 6-MP or azathioprine. So about 90 percent of the population has two good copies, and we can use the usual dose that we use. And in sort of weight-based dosing, for 6-MP it’s about a milligram to 1.5 milligrams per kilograms that we use. For azathioprine, it’s 2 to 2.5 milligrams per kilogram. If you have just one copy, then we use the standard dose. We’re going to cause your blood count to fall very quickly. About 10 percent of patients have just that one copy, that TPMT enzyme. And so, if possible, some of us feel that we should do that test before we start the medicine. But it’s not needed because we’ve been able to use these medicines before we had that test, but I think it gives us an added measure of safety.

The other test that we can use for Prometheus labs, and other labs are starting to do it, is to actually measure the metabolites of 6-MP and azathioprine. And there are two main metabolites that we look for. One is called 6-TG or TGN, and that’s the metabolite that we think has the efficacy, and it’s one of several metabolites. But if it’s in a certain zone, we think there’s more likelihood of response. Now if you’re in that zone, it doesn’t mean that automatically you’re going to respond. It just means the likelihood is higher. If you’re not in that zone, we may consider bumping up the medicine and try to get you in that zone. The other metabolite is called 6-MMP, and that’s a metabolite that seems to correlate in higher doses if you have that metabolite with liver toxicity. And so the usual things that we’ll monitor in patients on these immunomodulators are a blood count, a CBC and the liver function tests, LFTs.

Dr. Korzenik : There are a number of questions about alternative or natural therapies. We tend to focus on those that are best studied, that have the most data behind them. There are a number of compounds. So what do we mean by alternative therapies? Well, by alternative therapies, we mean things like aloe vera, different herbs and things like that. I don’t know if you’re familiar with probiotics. Antibiotics get rid of bad bacteria. Probiotics is the idea of using bacteria as therapy. All these things are very interesting and need to be researched more. There are some probiotics - not all probiotics are the same - that have been suggested to be beneficial and have been demonstrated as beneficial. But they’re not all the same. So just going to your health foods store and saying, “Oh, I heard about a probiotics,” and get something off the shelf, that’s not necessarily doing yourself any good. Aloe vera has been studied in ulcerative colitis. Again, it’s not any preparation, but there was a randomized placebo control trial that suggested a benefit. There are other things that are sort of on the borderline of alternative or not.

You may have heard about this therapy that’s coming around, which is worms, that Joel Weinstock has suggested that the reason why we have ulcerative colitis and Crohn’s is in our zeal to be clean we’ve gotten rid of our worm, that the worms in our intestines sort of act as a natural control of our immune system. We’ve gotten rid of it, and our immune system has gone haywire. So he’s actually, now actually, doing studies where he is giving people eggs of worms. But so far, the data look promising.

So all these things are interesting, and like any other therapy the promise of some of the herbal therapies is that they’ll give you some good without any harm. The problem is there’s a lot of snake oil out there. There are a lot of people on the Internet and other things that are selling things that are not effective and have no real evidence behind them.

Dr. Shah , what is the risk of recurrence after surgery?

Dr. Shah : Surgery is often helpful, but the problem is in Crohn’s disease it tends to come back. And it depends on how you define recurrence. Is it when we look with a scope? Is it when we look with a scope and biopsy? Is it your clinical symptoms? Is it needing another surgery? And so if you look at clinical recurrence, it’s actually low, on the order of 10 to 15 percent per year after surgery. But endoscopic recurrence is high, 80 percent or higher at the end of one year. And so what we’re moving to do is a lot more research and interest on preventing postoperative recurrence or delaying postoperative recurrence. And they looked at things like antibiotics, and the antibiotic they looked at is metronidazole or Flagyl. The problem with that is a lot of patients have side effects. They get numbness and tingling. It’s also not a fun antibiotic to take. You’re not supposed to drink when you’re on that. And long term, most people can’t tolerate it. So they’re looking at other antibiotics, but we don’t have good studies on that. They’re all looking at drugs, like the 5-ASA drugs. The 5-ASA drugs work a little bit but not all that great, so it’s hard to ask the patient to take a number of pills when the likelihood of it decreasing the disease from coming back is low. And most studies will put it - you have to treat about 15, 16 patients with a 5-ASA drug for one patient to benefit. And then, we’re looking at immunomodulators like the 6-MP and azathioprine. And those drugs seem to decrease relapse rate. There is a recent study that came out, but it’s an immunomodulator, and you have to monitor. And some patients may do well after one surgery for many years, so it’s hard to ask somebody to take that. That being said, a lot of us are advocating at 6 or 12 months after surgery going in, looking with a scope and seeing if there’s a lot of recurrence. If there is, [we're] going more toward the aggressive therapy like the immunomodulators, and if there is very minimal recurrence, then [we're] either doing nothing or using a 5-ASA drug.

Dr. Korzenik : Dr. Leleiko , do you recommend any particular monitoring of any vitamins or minerals?

Dr. Leleiko : I think it depends on the situation for each individual patient. You individualize. Patients will have their blood count monitored and see. You want to measure hemoglobin, the blood count, and that’s a measure of iron. When I do routine blood [checks], I do check iron stores, which I find to be more relevant than just the iron level. So I think iron is very important to check when blood is drawn. You don’t want to draw excessive amounts of blood. It’s a sure way to guarantee to have deficiencies of some of these things.

Part of the problem with many of the vitamins and many of the minerals that people would like to assay is that the assays, the levels that you see, are not really reflective of what the biological situation is. They may reflect recent intake but won’t tell you exactly what’s going on beyond that. It’s important for me when I see, if I know a patient has Crohn’s disease or I suspect it, I do check a vitamin B12 because patients do, most of the water-soluble vitamins are absorbed pretty readily throughout most of the intestine and, therefore, should not pose a problem. Vitamin B12 is absorbed just in a very specific portion of the intestine, the portion called the terminal ileum. And you heard Dr. Korzenik talk about terminal ileitis. So this is an area where Crohn’s disease is likely to occur. About three-quarters of patients with Crohn's disease have some disease in their terminal ileum and colon. When we’re born, if a baby is not premature or otherwise ill, the child has a significant amount of [vitamin] B12 on board, and if deprived of [vitamin] B12 will not develop deficiency for two to three years. So if somebody is well-nourished and develops Crohn's disease in this area, they may not develop a deficiency right away. But it is important to keep in mind that that is something that can develop. So I think [vitamin] B12 is important. Some individuals look carefully at zinc though I’m not certain that one can monitor zinc as effectively as you would like. And sometimes there are surrogate markers. Some of the enzymes that we get, such as liver function studies, again we monitor that one. That’s a specific thing that I’ll do for some patients, not generally.

So in terms of minerals, a serum calcium has no meaning in terms of whether or not somebody is getting adequate calcium. Iron, I mentioned, zinc, on occasion. Zinc is something to keep in mind in certain circumstances. And a zinc supplement is quite reasonable for some patients though I generally don’t recommend it across the board for everybody. If you are going to take a multivitamin with minerals, then we want to make sure that it has folic acid because folic acid levels may be diminished for several different reasons. I would rather they be taking folic acid. [Vitamin] B12 I would monitor. Vitamin D: Vitamin D is important, but it depends on what you’re actually monitoring. The normal level of vitamin D that we measure reflects how much vitamin D is in our diet and is absorbed. I think that we want to make sure that patients are getting adequate calcium and vitamin D for a variety of reasons just like you would want to make sure that it’s in the diet. I don’t routinely check 25 hydroxy vitamin D, which is a form that we take, unless I’m concerned that somebody has particular evidence of fat malabsorption or specific disease in the terminal ileum, so that’s not a routine test, but it is something that I’ll do.

Other vitamins: Vitamin A, I don’t routinely check. [Vitamin] D, I mentioned. [Vitamin] E, there is not a good test for vitamin E. Vitamin K, there’s a test for, but we would rarely use it. If somebody was on a lot of antibiotics for a long period of time, there is a test called a prothrombin test. But it’s not a routine that I would do. The water-soluble vitamins, they’re less reliable other than [vitamin] B12. The minerals, I think I’ve covered.

Dr. Korzenik : Dr. Shah , what can you tell us about the long-term safety of Remicade [infliximab] and 6-MP?

Dr. Shah : That’s the 64 million dollar question, I guess. So far, the safety record, let me try it with the 6-MP, and this applies also to azathioprine. Long-term safety is good and if it’s working, then the recommendation of most GI docs who take care of IBD patients is to stay on it because coming off of it, there’s the high risk of relapse. So far, most studies suggest that there’s not an increased risk of cancer although there have been some studies that suggest maybe a slightly increased risk of lymphoma, particularly in lymphoma related to Epstein-Barr virus. Infections, we know about. We monitor the blood counts carefully. So that’s 6-MP and azathioprine.

Infliximab has been around since 1998. [It was] FDA-approved in 1998, and clinical trials go back further. And so it’s a relatively new drug. If all the publicity about the COX-2 inhibitors, the Vioxx [rofecoxib] and Celebrex [celecoxib] has taught us anything, [it] is that we need to be careful. These new drugs are great, but sometimes it takes thousands and hundreds of thousands of patients on a drug for a long period of time before we realize side effects. That being said, I think it’s been an important advance, and most patients do well with it. Long-term side effects: We haven’t seen a huge increase in cancer, and that’s very reassuring. There have been case reports of lymphoma, but again it’s not clear that it’s higher than would be expected in that population followed over time. Infections: We certainly see more infections in patients on infliximab, but we sort of again look at the risk/benefit ratio, and if somebody is doing well, we continue. The studies that have been done have only been done for a year out, and so the question is what to do if somebody has been on infliximab for a year. Do you keep going? And what most of us are doing is if somebody is doing well without side effects, we keep using it. We don’t start with infliximab early. We use it for somebody who’s failed the other things. And then if we’re using it, we keep going with it. And, frankly, I’m a little bit nervous, but there are a number of years of data now, so I’m less nervous than I was a few years ago. And so if it’s working, I stay on it. And then if it either stops working or somebody has a side effect, we’ll stop it. And there is a registry called the TREAT Registry where they’re keeping track of how patients on it are doing and looking at the development of any side effects or problems. [Are there] any other comments on those two?

Dr. Leleiko : I would just add that if you’re 40 years old or 50 years old and likely you’re at-risk to develop a side effect 40 years down the road, I think that you take that chance if you see fit. But if you’re 10 years old or if your patient is 10 years old, those risks are quite a bit. The way you factor that equation is quite different. That having been said, I essentially agree with what Dr. Shah said.

Dr. Korzenik : People were asking about mesalamine, sulfasalazine - is it safe to be on these for life? Yes, with sulfasalazine, you would want to be on folic acid because it can block the absorption of folic acid.

Are they all safe in pregnancy? Yes, as far as we know, they’re all safe, and they all have sort of interchangeable benefits. Maybe there’s a rare patient who wouldn’t respond to one that would to another.

A number of people asked about side effects, and typically over 95 percent of people tolerate these well. But perhaps 1 percent or so will have a bad side effect, meaning that they actually take the sulfasalazine or Asacol [mesalamine] or Pentasa [mesalamine], and they get worse. And so, first of all, it’s important to recognize that, but occasionally it can actually make somebody worse. But then the question is well, if that happens to one of them, are you going to get it to another one? In all likelihood, you will, and it probably means that if you’ve tried one or two or three, you’re going to get them to all of them, and that class of drugs is out for you. And then what are you going to do? Well, it depends on how severe the disease is. If it’s very mild, you might try to tinker with some other things that are relatively mild. If it’s more severe, you’re still going to need something for maintenance. And if you’re having flares every so often, you might even have to go onto something like 6-MP, even if you’re not having a whole lot of symptoms because you need something to keep yourself under good control. So that particular side effect should be looked for or understood and taken care of.

Dr. Leleiko , maybe this isn’t the right question for you as a pediatrician, but is it okay if you have Crohn’s or ulcerative colitis to have a glass of wine or beer once a week?

Dr. Leleiko : If you have a glass of wine or a bottle of beer or a glass of beer and you get sick afterwards, no. But if you have it and you don’t get sick, yes.

If you’re on Flagyl, if you’re on metronidazole, I would have to add that that’s a drug that was actually developed with the goal of counteracting the metabolism of alcohol, and so it didn’t work quite as well as people had originally anticipated. It turned out to be a much better antibiotic. But many people will get ill even with one drink. So you have to be fairly careful of that. But I’ll leave the other comments to my adult colleagues here.

Dr. Shah : I think it’s fine. There are a couple of concerns. Obviously, moderation is key. We used to say that with azathioprine and 6-MP you can’t drink alcohol. It turns out that that’s not true. Drinking a couple of glasses of wine per week or a couple of beers per week is safe with 6-MP and azathioprine. Actually, Dr. Present has presented that data at one of our meetings. The labeling of the drug in the PDR will say no, no alcohol with that. Obviously, don’t drink and drive, and that’s it.

Dr. Korzenik : And how about coffee?

Dr. Shah : [Coffee is fine] as long as it’s not giving you diarrhea, and caffeine can increase GI motility. And so I don’t think it causes a flare-up of your Crohn’s or colitis, but it can increase GI motility, give you more bowel movements. If you’re not having a problem, I wouldn’t necessarily decrease your coffee intake. On the other hand, if you’re going to the restroom a lot and we sort of evaluated and your colitis or Crohn’s is under reasonable control, one thing to do is cut out caffeine.

Dr. Leleiko : I would add that for many patients where there’s a question of lactose intolerance, having a piece of cake or something with a lot of milk in it, pie, whip[ped] cream, or whatnot, may or may not give them symptoms. Having it with caffeine may increase their symptoms. So people should be aware of that and act accordingly. But there’s no absolute contraindication to using these things.

Dr. Korzenik : Is it unusual to have no symptoms at all until age 64 when a perforated ileum reveals Crohn’s?

Dr. Shah : With perforation, you don’t really have any warning signs until it happens, and then the bacteria that are normally inside the intestines spilled out into your peritoneal cavity, and you get severe pain. It’s not subtle. I mean you’re in the emergency room. You’re not thinking, “Should I not bother my doctors? Should I, you know, take it?” You know it’s severe. You end up in the emergency room. Now if you’re on steroids or other things, your symptoms may be masked, okay? And so somebody who is on steroids and complains of mild belly pain sometimes will be a little bit quicker to get a CAT scan to look for these sorts of things. And there are, unfortunately, not very many warning signs to that. So, unfortunately, if that happens, that’s usually surgery. Occasionally, we can get by without surgery and use antibiotics and bowel rest. But usually if there’s a perforation, that means automatic surgery to close the hole, decontaminate the intestine.

Dr. Korzenik : Dr. Leleiko , here’s a question about someone who has relatively mild, indeterminate colitis, and blood work is normal. Growth rate is normal. Bone density is normal. And the question is how do you treat it? So the broader question is how do you decide how aggressive to be with therapy?

Dr. Leleiko : I think that there’s a whole lot that one could say about that. The goal, in general, is for somebody to lead a normal life. If they’re leading a normal life, then you want to accomplish that with the least amount of medication possible. And if somebody was doing well without medication, it would be a very worthwhile question and not an immediately obvious answer whether or not they should be on any medication. If I thought that a patient had inflammatory bowel disease and was doing well, I would try to convince them to remain on their 5-ASA compound at this point in time based on the belief that this may decrease the risk of flare-ups. There is evidence to that. But if a patient had very mild disease, it goes back to the question, do you think they have disease? Is there something else? But I think that’s something you get in to discuss with your physician.

The definition of indeterminate colitis varies somewhat from place to place and from pathologist to pathologist. And sometimes it’s a matter of conviction, and sometimes it’s a matter of religion, so to speak. You know, I don’t want to commit myself one way or the other, so it’s indeterminate. But, so, I think a straightforward as it might be, it’s a little bit tricky. The guiding principle for me is that I try and maintain the person a normal life with the least amount of medication possible. If they’re leading a normal life without any medication, that’s not bad. But I probably would have that patient, if I thought they had inflammatory bowel disease, on a 5-ASA compound.