Dr. Kane: Dr. Bousvaros, what’s the risk of a father passing this along to their child?

Dr. Bousvaros: That’s one of the more common questions that we get asked in pediatrics because we do know that this is in part a hereditary disease. But, again, it’s not strictly speaking a genetic disease. Genetics don’t mean you’re going to get the disease. Genetics, just like with heart disease, like with migraines, like with a number of conditions, means that you’ll inherit a risk for the disease. We know that if one parent has either Crohn’s or ulcerative colitis, the risk of any individual child getting it over the course of their lifetime is about 3 to 5 percent. Or looking at it the other way, the good news is it’s 95 to 97 percent chance your child will not get Crohn’s disease if you have the illness. Now if you have two parents that have IBD, that risk goes up to about 10 to 15 percent, and, as of yet, we don’t have a good way necessarily of preventing the disease.

Dr. Kane: There may be ways by introducing parasites or probiotics or other things that we may be able to decrease the risk of developing Crohn’s or colitis. Those studies are very hard to do because you need lots of long-term follow-up. But, I think, over time, as we learn more, there will be more focus on prevention because these diseases may indeed be, in fact be preventable.

Can you talk a little bit about, more about the joint symptoms of the arthritis and something called sciatica? Is that related?

Dr. Sands: Sure. So [do you mean] not talking about the density of the bone, per se, but now the joints themselves?

Dr. Kane: Right.

Dr. Sands: It’s one of the more common manifestations of inflammatory bowel disease outside of the bowel itself - would be someone to have joint aches, and very often it may be a minor thing. It may be aches and pains in the hands. It may involve larger joints, particularly the knees or the hips. It can also involve the upper extremities, the arms, the elbows, the shoulders. But for the larger joints and for the joints that are not in the midline of the body, those are the kinds of joint aches that tend to go with a flare. And, in contrast, there are joints in the spine as well. There are some people who may have inflammation of those joints as well as the hip joints, not the hip joints themselves but the sacroiliac joint, between the spine and the hip bones and the back. And that can feel like sciatica. And that particular kind of arthritis doesn’t necessarily go hand in hand with a flare. It can [go hand in hand with a flare], but it can also run a course completely independent of a flare of the colitis or the Crohn’s.

Dr. Kane: And what about prednisone, can you use that to treat it, or can it cause these problems?

Dr. Sands: Well, prednisone probably would make the joints feel better, but for all the reasons that you pointed out we would prefer not to use prednisone as the main treatment. Generally, we try to treat with the other things that treat the primary inflammation in the bowel itself and then hope that the joint aches are going to get better.

In particular, as Dr. Kane already said, sulfasalazine may be better than some of the other 5-ASAs for treating joint aches of the large joints, not the midline ones like the spine. And the other interesting manifestation that we sometimes see is people who’ve been on steroids for a long time can get joint aches as they taper down. And that may be because they're relatively deficient in the steroids that you would normally be producing on your own.

Your body is always producing its own steroids. And if you’re on steroids for a long while at higher doses, your adrenal glands, which make those steroids naturally, are sort of turned off, and they sort of lose the capacity to make their own steroids. But as you get to lower and lower steroids, usually doses less than 10 milligrams, you may have lots of joint aches, and that is a sign that you are hypoadrenal, or you’re not making enough of your own natural steroid. And that tends to go away over time. But if you’ve been on steroids for 20 years, it’s not reasonable to expect that you’re ever going to necessarily be able to make that again.

Dr. Kane: Five different people have asked about alternative therapy, not necessarily using the word "experimental" but alternative or natural therapies.

Dr. Bousvaros: There is a lot of interest in using more natural therapies for these diseases. I mean, they are chronic diseases as Dr. Kane went into. All of the medications we have, which we’re pretty comfortable in using, do have the occasional side effects. Some [have them] more than others, and some of these side effects can, at times, be quite serious.

We actually did a study at children just looking at what percentage of our children were being given alternative therapies. And the proportion is similar to that we see in adults, which is about 40 to 50 percent. So about half of patients are taking megavitamins, herbal preparations, probiotics or all these things. When you take these treatments, I think you have to ask yourselves two questions. One is, are they safe? And the second, is there any good evidence that they work? Most alternative therapies that we have are relatively safe. There are some that can occasionally cause diarrhea, cause gastritis and cause stomach upsets, especially some of the herbals. And you need to be careful with those. I have a big compendium of what these herbals are, what’s in them and what their side effects are. And often people taking them don’t know what the side effects are. So you do have to know that. The second thing, unfortunately, is that very few of these herbals or probiotics, or other things have really been tested in carefully controlled manners.

If you’re going to take, or want to take, an herbal or complimentary preparation, number one, discuss it with you doctor. Let your doctor know what it is. And at least look it up yourself, or have them look it up to make sure there are no side effects or drug interactions.

Secondly, don’t stop taking your regular medications. I mean, I think what happens is some feels pretty good, their worried say, about the long term side effects of 6-MP. So they stop their 6-MP and start taking an herbal. And you’re probably going to get sick if you do that.

The third thing is to be as critical of the herbal products or of the complimentary product as you are of your regular medicines. Look at these things. Have they been tested in Crohn’s patients? What preparation are you using if you’re taking a probiotic or the bacteria in that preparation even alive? Because a lot of this stuff that sold at GNC and CVS, the bacteria is actually dead in there. So you have to be careful. Now, moving onto certain specific things, I think there is some data to suggest fish oil might help Crohn’s and colitis. It’s certainly marketed heavily. It’s pretty safe. Again, that’s one I would feel comfortable [with].

Dr. Kane: Maybe [it's] not [good] for the breath but probably okay for the gut. That one we feel pretty good about. Someone asked about vitamin E. I saw [that] was one of the cards. Again, medium-dose vitamin E, we think, is relatively safe. We don’t know if it works. And probiotics, which are so-called good bacteria that people feel might either control infection or down regulate inflammation, the results are all over the map. There’s a lot of conventional medical interest in probiotics. There are a lot of studies being done. One particular probiotic called VSL #3 has been shown in carefully conducted medical studies to help pouchitis. There are less well-conducted medical studies of other probiotics that suggest some efficacy. We recently finished a controlled trial of a probiotic called lactobacillus GG in children, and we compared it to placebo for kids with Crohn’s. And we showed that when you take it on top of your regular medications, it really doesn’t help above and beyond your regular medicines. My advice is take the stuff you know works. If you want to try something else, talk it over with your doctor. Make sure it’s safe and also wait for more studies to come out. The National Institute of Health has a huge interest in all these different therapies. They’re pushing very hard for doctors and scientists to do studies in these areas and hopefully, over the next five to 10 years ,we’re going to find which ones of these make Crohn’s worse, which ones make Crohn’s better and which ones don’t work at all. And I think the same is true of ulcerative colitis.

Dr. Kane: VSL #3: VSL stands for very special lactobacillus. That’s what the VSL stands for. And it’s preparation number 3 because one and two didn’t work. So there’s nothing magical about VSL 3. It stands for very special lactobacillus. For adults who are interested in some of the alternative therapies, how do you feel about that, and what maybe are some of ones that you’ve heard about?

Dr. Sands: The things that I feel there are some data for, again, include fish oils, omega-3 fatty acids are probably the active part of that, and there are other forms of, plant forms, of omega-3 fatty acids that have not been well-studied, but some patients do try those. I think some patients discern some benefit [from] probiotics although again the only situation for which probiotics have clearly been shown to be advantageous would be in pouchitis. With this particular preparation, VSL 3, there is a little bit less data concerning maintaining remission using other preparations.

Aloe vera is another thing, which recently was shown, in a randomized control trial that was blinded, which is sort of the Cadillac version of a clinical trial, perhaps to be effective although there have been other studies, which have been not so positive with that, clearly, a harmless thing. The only additional bit of advice that I give my patients is to be critical of the source of these things. In other words, who’s trying to sell you things? All too often what I’ve found with my patients is the practioner who is telling you that you should take this certain preparation stands to make an enormous profit from your buying this preparation. And that always makes me just a little bit suspicious of their motives, when there isn’t necessarily good scientific data.

Dr. Sands: I’ve had more than one patient tell me that when they go on a low-carbohydrate diet, at least their symptoms feel much better.

Dr. Kane: Elaine Gottschall has written this book, describing this diet. The diet is supposed to work for all sorts of bowel conditions. But, in a handful of Crohn’s patients who have seriously done this, and it’s a very difficult diet to do exactly the way she says.

I’ve had a handful of patients who actually really do feel better. And not only that, I can track their laboratory values as C-reactive protein, which is a measure of inflammation. There is no faking this. It’s a blood test tracking down, down, down, down. So we actually have a very small study looking at this very diet, in a very controlled, scientific fashion.

Dr. Bousarvos: And I would emphasize there have been a number of studies that have been done in children of a very restrictive [diet] in Crohn’s disease. Specifically, you don’t let that child or young adult eat anything. You place a tube down their nose, and you give them what’s called an elemental or polymeric formula - basically, like Booster, Ensure or some more specialized, more broken-down formulas. And we know that it doesn’t work quite as well as steroids, but a significant number of patients - probably 60 to 80 percent - do achieve a remission with that kind of treatment. The problem is, I mean, are you going to live like that your whole life? And the answer, of course, is no.

So once people start eating again, typically their Crohn’s flares up. We’re out to help the bowel and control inflammation, but we’re also out to help people lead normal lives. And I think this is one area, especially diet, where I have parents who are really getting into fights with their teenagers about what they can and can’t eat.

If you’re going to try an alternative or dietary therapy, you should do it with a doctor’s supervision. You need to be very committed to it, and you also need to have the common sense to say this is or isn’t working for you. That’s the bottom line.

Dr. Kane: I’m going to answer a question here. And this is regarding a blood test to determine if [a patient] should be starting on a medication. I think it’s a good question in general terms about what we know about genetics and what we know about therapy and how the two may mesh. And 6-MP and azathioprine are metabolized by the body, by very specific enzymes. And it turns out that those enzymes are genetically determined and that for the majority of people, it doesn’t even matter that you’ve got these enzymes in your body. But it’s sort of interesting that we do [have them].

Patients who have more normal genes where this enzyme works normally, there is no problem with giving them standard doses of azathioprine or 6-MP. There is a small minority of patients who have abnormal genes, where the enzyme doesn’t work as efficiently as it’s supposed to, and that if you give these drugs that, it’s not metabolized, and so a lot of the drug hangs around. And so they are higher risk for some of the side effects because it’s there in otherwise what would be higher doses, or higher levels at the doses that are pretty standard. So there is a blood test that’s available that your doctor may do to sort of see where genetically you stand in terms of being able metabolize those drugs. And then that can help to figure out what dose is going to be appropriate for you and to keep you from having a lot of side effects. I think, would you agree that that’s where the question’s going?

Dr. Bousvaros: I would emphasize that, in my opinion, and I appreciate Dr. Sand’s opinion. I basically have made it mandatory to obtain this genetic test, to let you know how you’re going to break down 6-MP or Imuran [azathioprine] at the time of or before you start that medicine. And the reason why is, according to the literature, 1 in 300 patients can’t break this down at all. And if you give this medicine, you could get irreversible or very severe bone marrow suppression.

I was very unlucky early on in my career, before these tests had become widespread, actually had two patients like this who developed very severe bone marrow suppression, couldn’t make white cells, and couldn’t make platelets. Each of them spent about a month in the hospital. And then we went back, and we did this genetic testing, and we found both of them were deficient. They couldn’t break down 6-MP. Since that time, I’ve found a third patient. Now the odds of me finding three patients who don’t break it down, if you do the math, is about one in 90,000. So it may be that this is more common than is believed, but with a very simple blood test you can keep your patient from getting very, very sick. I think it’s worth the cost. It’s $200 to $300, I would just do it.

Dr. Sands: It’s about 200 bucks. And I do exactly the same thing that you do. Every patient that I start on azathioprine or 6-mercaptopurine gets this TPMT test, the enzyme test.

Dr. Kane: It doesn’t make much difference if you’re already on the drug, then you’re tolerating the drug. But the point is to do it before you get put on the drug. And, in fact, there is at least one good scientific paper showing that testing for this is cost-effective. Even though it costs a couple hundred dollars, it actually ends up saving whoever, the community at large, money because you prevent these really awful complications that however [are] very rare.

I’ve got three or four questions here about drugs that seem to wear off, in particular, infliximab. But some of the others that they take long term, is there a risk for them to wear off if they’re on a 5-ASA, or is this particular to some of these new biologics?

Dr. Sands: Any drug effect potentially could wear off. And the reasons that drugs may lose their effectiveness, there are actually a great number of reasons why they can lose their effectiveness. Biologically, it could be that you handle the drug differently over time, your metabolism changes, and you’re not handling the drug in the same way, and you’re losing more of it. You don’t have high enough levels of it. It could be that biologically, your body, if the drug blocks a certain pathway that causes the inflammation, inflammation occurs by a certain mechanism and that’s how the drug, what the drug is working on. The body is very clever in finding ways of working around that blocking point and finding new ways of creating new inflammation, if that’s what’s destined to be.

In the case of Remicade [infliximab], there’s a very specific reason why people may lose their response. What happens is people develop antibodies against Remicade, and that is because, in part, you’re giving this protein that is a foreign protein. Part of it is very foreign. It’s actually a mouse protein sequence. And so your immune system looks at this and says, "This looks very strange, and I’m going to try to get rid of it by forming antibodies against this protein and clearing it out of the system."

Dr. Kane: How long does that take?

Dr. Sands: Well, it’s generally not with the first infusion because it requires exposure of the immune system to it at least one time. And then the second time that your immune system sees it, there is this memory immune response. Now this clearly doesn’t happen in everyone. But we do know that there are a number of risk factors for this to occur. One is if you interrupt treatment for long periods of time - say more than 8 or 12 weeks - that you’re prone to have these antibodies form. If you take Remicade without also taking either steroids or a drug like 6-MP or azathioprine, Imuran or methotrexate, you’re more likely to have this occur. And so it’s not that uncommon in those circumstances for people to lose their response - or at least to partly lose their response, meaning instead of going eight weeks, going well, you’re going six weeks or you’re going four weeks before you start having return symptoms.

Dr. Kane: So can people be on Remicade for years if they respond?

Dr. Sands: I certainly have some patients in my practice who’ve been on it for the whole time that the drug has been on the market and even before then were on it in clinical trials. So, yes, it is possible to do that. But, certainly, people worry about the expense. That’s not my problem. That’s the insurance company’s problem. Hopefully, it’s not my patient's problem because if anyone had to pay out of pocket, that really would be a problem. But people really worry about the side effects. This is a powerful drug. It does suppress the immune system, and we know that there is an increased risk of infections. Some of these infections, although rarely, may be fatal. That’s a well-established fact that you have to discuss with your doctor before you go on the medication. And so there’s this desire to not be on the drug because of the side effects as well as to be on the drug to prevent losing response to the medication.

You have to think about that. But I would be surprised if it’s very different. I keep a very high threshold for putting someone on Remicade. In other words, most of my patients will have been through 6-MP or azathioprine or methotrexate or before they ever get to go on Remicade. And if they're not responding to that and surgery is not a good option for them, then, yes, it’s worth taking those small, but definitely there are risks with Remicade.

Dr. Kane: Dr. Bousvaros, please comment on the lack of diagnosing IBD in children in the developing countries.

Dr. Bousvaros: We don’t know precisely what causes Crohn’s or colitis, but we do [have evidence], and I think there’s pretty good evidence now that it’s more common in the developed world, particularly Northern Europe the U.S. and Canada, than say in Africa, India, Pakistan, other countries. And that seems to be true not just of Crohn’s disease but of a number of other autoimmune diseases.

The developing world, Asia, Africa, tends to have a lot of infections - salmonella, tuberculosis, all these things. Whereas, in your part of the world, perhaps with antibiotics, with immunizations, with better hygiene, we have fewer infections. But we seem to have a higher prevalence of autoimmune disease, and that’s not just Crohn’s, it’s multiple sclerosis, it’s asthma, it’s food allergies and all these different things.

So one hypothesis that’s developed - and again this is not proven by any means - it’s perhaps early exposure to infectious organisms a.k.a. worms or other bacterial infections or measles or T.B. or, or viruses seems to perhaps stimulate the immune system. But then as you’re resolving the infection, another arm of the immune system is coming up and building up a tolerance. And when you have a number of immune system cells that generate tolerance to infection, then that result is you have fewer of these autoimmune diseases. So it is a real finding that Crohn’s and colitis are more common in the developed world than in the developing world - it’s not simply because they can’t recognize cases, and this is the fear that people think about.

Dr. Sands: The worms are interesting. The idea is that all through historic times, probably all mankind were infested [with] worms. It just was an unavoidable thing until we had hygiene occur the way we have it now. And it’s clear that having those worms certainly has some negative effect in many cases. But also, there may be some positive effects on the immune system. It programs the immune system in a certain way that may decrease the responsiveness to certain kinds of things in the environment that we may encounter, including possibly the bacteria that all of us have in our colon, which is what we think may be one of main things that the immune system is overreacting to in Crohn’s disease and ulcerative colitis.

Now it’s a whole other question to consider whether taking worms as a therapy could actually change the immune response in the intestine in a therapeutic way. And there is an investigator who was based at University of Iowa, Joel Weinstock, where they have a lot of pigs, and he developed this notion that you could give pig whip worms, which are not harmful in man. But, sort of, if you take the eggs for these worms, which are teeny little microscopic eggs, and you drink them down, they hatch in your intestine. They live there for about three weeks, and then they're shed. They don’t invade. They're not causing any sort of illness or disease, and the hope is just having them just sit there in that environment in the intestine would change the immune response and bowel in a favorable way. And now, there are studies, even blinded control studies, that would suggest that these may be modestly effective although these are very small studies. They're early phase studies. They really need to be reproduced again. They need to be validated in a way that we consider completely thorough and scientific. But they seem to be completely harmless as well. It just so happens that, I hesitate to mention this, but the guy who developed this, Joel Weinstock, is moving to Boston and may, in fact, already be here.

It’s not clear. It may actually hit the market as a - not a pharmaceutical not a drug - it may be like a food supplement kind of thing, so you might be able to buy it at your GNC.

Dr. Bousvaros: Well, you can actually buy them now. If you looked them up off the Web, you can get them directly from the German company. I think, and again this emphasis is a potential treatment that might help some patients. We don’t know how well it works. We don’t know what the long-term side effects are. It definitely warrants further study, both in terms in safety and as far as effectiveness. Every three or four years, there is another great white hope. And, again, if you’re doing okay and you’re happy on the medicines that you’re on and you’re feeling well, you don’t necessarily need to go out there, looking for other things. The goal here is to keep you healthy. But if it’s early on, you have questions, you have concerns about safety. I think, again, it’s okay to bring this up with a responsible physician and an honest physician, and hopefully they’ll go through a little bit of the pros and cons with you. The truth is it’s interesting that all the data is very preliminary, and we just need more time. Be extra careful with new treatments.

Dr. Sands: You don’t necessarily want to be the first on the block.

Dr. Bousvaros: Exactly, [you don't necessarily want to be the first one] unless you’re participating in a study. Because if you’re participating in a clinical trial, you’re not only learning yourself about something, but you’re helping other people learn about this. Every person who participates in a clinical trial, it always ends up you’re not doing as much for yourself as you might be doing it for your children or for your relatives who might come down with this disease in the future. Because you’re not just learning if a drug works on you, you’re helping others find out if it works for everybody.

Dr. Kane: Dr. Sands, what’s the connection or the association between marijuana smoking and IBD?

Dr. Sands: I don’t know that that’s actually ever been studied, but, anecdotally, some of my patients feel better and some of them feel worse. So what is your experience with your patients?

Dr. Kane: It’s a very good anti-nausea therapy. It’s a very good appetite stimulant, and it’s also good for pain. So in some patients, they seem to derive a benefit, but I don’t think that their lungs are benefiting. Their Crohn’s may be [benefiting].

The patients say, “Listen, I’ve been well. I don’t want to take medicine anymore. Why do I have to do it?” In a study that we did in Chicago, we took patients who had ulcerative colitis and who were well at the time that we started studying them. And we just watched them over two years. And we asked them, “Do you take your medicine?” [They say,] “Oh yeah, I take my medicine.” And we watched to see what happens to their disease. Well, unbeknownst to them, we also called their pharmacies to find how much they were refilling. And, that it turns out, over two years that the patients who really were taking at least 80 percent of their medicine, we weren’t looking for 100 percent here, we were looking for 80 percent or better. So they were adherent, and at the end of two years over 93 percent chance of still being in remission. Those patients who weren’t taking 80 percent of their medicine, and it turns out they were taking far less, then over two years there was only about 30 percent of those patients had a chance of still being in remission. And the difference between those two lines is fivefold. So that if you want a reason to still take your medicine, you have a fivefold increased chance of still being in remission two years later if you take your medicine.