Commentary

DR. LACY: Let’s tackle the easy one first, and I think that’s the role of colonoscopy. Several studies have pointed out that if patients meet Rome III criteria in the absence of warning signs, the utility of a colonoscopy would be very, very low.

We all agree that if the patient is older than 50 years, and ≥45 years for African Americans, even if there are signs of IBS and you’re pretty confident about the diagnosis, a colonoscopy is still required for screening purposes.

The utility of a colonoscopy in a younger patient—younger than 45 years—with classic symptoms of IBS in the absence of warning signs is extremely low, and I don’t generally recommend that.

One caveat, of course, is that as clinicians, we’re always double-checking to make sure that our diagnosis is correct. We review the patient, see them in follow-up, and make sure that our treatments are appropriate in helping the patients. But if things aren’t making sense, and if the patients aren’t responding, we’ll always go back and question whether the diagnosis was correct, realizing that in some patients with nonconstipated IBS, what appears to be IBS might actually be microscopic colitis, including lymphocytic colitis or collagenous colitis, and celiac disease.

That’s a nice segue, and I think testing for celiac disease is really quite controversial. We know from the study published in Lancet in 2001 by Sanders and colleagues²⁶ that patients with IBS were apparently 5 to 10 times more likely to have celiac disease than those who did not have the disease, and there was a real level of enthusiasm to test nearly all patients with IBS to look for celiac disease.

We also know from the American College of Gastroenterology (ACG) guidelines²⁷ published in 2009 that for patients with diarrhea-predominant IBS or mixed IBS, meaning the nonconstipated IBS patterns, testing for celiac disease is recommended. Keep in mind, of course, that the prevalence in the United States is estimated at about 1%. That being said, I think the best recent investigations were the multicenter trials involving Bethesda Naval and Michigan.²⁸ This multicenter trial involved nearly 500 patients with nonconstipated IBS and nearly the same number of healthy controls who were admitted for routine colonoscopies, and the prevalence of celiac disease was virtually identical. It was 0.41% for IBS patients and 0.44% for controls. Thus, I don’t routinely recommend testing for celiac disease, although if someone has nonconstipated IBS symptoms and they don’t respond to what I think is appropriate initial empiric therapy, at some point, I may check them.

DR. CASH: So, Drs. Harris and Chang, what’s your take on the celiac question and should we be testing for celiac disease in patients with symptoms consistent with nonconstipation IBS?

DR. HARRIS: I find that in patients in whom bloating is a disproportionate symptom, it might be worthwhile to check for celiac disease and review the family history. I think we’ll get into this discussion a little more detail when we discuss the diet, but we also have to think about gluten sensitivity. It’s become more challenging to sort out who truly has celiac disease and who may have gluten sensitivity, and I think those are important considerations.

DR. CHANG: I agree. At this point, the evidence suggests that we should still screen for celiac disease because it is cost effective, since the treatment is so different from that for IBS.

I think for microscopic colitis as well, it would be nice to do a similar cost analysis to determine whether we should be screening for it more than we do because it’s actually fairly prevalent in the population of IBS patients with diarrhea, particularly in middle-aged women, as Brooks’ study demonstrated.²⁹

DR. HARRIS: The prevalence in the Western world is estimated to be 1 in 132 patients.³⁰

That’s a fairly common occurrence for a disorder, so I think the jury is still out. A study previously suggested that celiac disease is more common in IBS patients, and one study suggested that it isn’t so.^27,28,31–33 I think that that the decision to screen or not to screen is not clear yet.

DR. CASH: Yes, it’s still a very controversial issue. Dr. Chang, once the diagnosis has been made, what is the natural history of nonconstipation IBS in terms of surgery rates or the change in diagnosis, perhaps even the risk of developing other disease, which seems to be a common concern of our patients?

DR. CHANG: There was one study that evaluated the natural history of IBS many years ago.³⁴ It reviewed multiple other studies where they followed patients from 6 months to 6 years after the original IBS diagnosis, and they found—consistent with the data that you and others have presented—that the prevalence of determining an alternative diagnosis to IBS is very small.³⁵ It’s about 2% or slightly more than that.

Up to 50% of patients will actually have unchanged symptoms over the years. About 2% to 18% will have worse symptoms.³⁴

If you follow-up the IBS symptoms over time, about a quarter to a third of patients will actually become symptom-free. And we know from post-infectious IBS longitudinal data that the prevalence of IBS declines over time.

In general—and this is something that I tell my patients—the symptoms usually fluctuate over time and much of what we do to treat or manage the symptoms can help to alleviate them to a certain extent. But even when the patients are working hard to manage their symptoms, they can still have symptom flares, although they may be less frequent or milder, and that’s just part of the natural history.

For the bowel habit subtypes, studies have shown that if you follow-up patients, over time, their subtype of IBS can actually change. One study by Doug Drossman and colleagues³⁶ followed IBS patients for over 1 year. They evaluated the symptoms every 3 months in that 1 year and found that 75% of IBS patients actually had a change in their bowel habit subtype over the 1 year.

You would typically see the IBS constipation and the mixed IBS interchanging from one another, and the mixed IBS would also interchange with the IBS with diarrhea. It was less frequent for an IBS with diarrhea to change into an IBS with constipation.

DR. CASH: Certainly, the changing clinical picture of IBS is going to make the evaluation and management of those patients more challenging as well.

Let’s shift over to the topic of treatment. Dr. Harris, you mentioned a few moments ago the role of gluten and perhaps gluten sensitivity. So what role, if any, does diet play in the treatment of nonconstipation IBS?

DR. HARRIS: I think that diet is probably the forgotten factor. Patients have, for years, been telling us that when they eat certain foods, they seem to experience more severe symptoms. They tell us that onions, garlic, fatty, and richer meals cause the symptoms to appear. In fact, Albena Halpert did a study³⁷ that looked at factors in diet that have helped patients, and patients reported that if they ate smaller or less fatty meals or avoid lactose, their IBS symptoms improved.

So, lactose intolerance is a fairly common symptom in the population, in general, and the 2009 ACG guidelines quote a study that showed that the prevalence in the population is about 25%, whereas in the IBS patient population, it’s somewhat higher, around 35% to 38%.³⁸

Patients find that when they avoid lactose, sometimes, there is an improvement in their symptoms of bloating and diarrhea.

In practice, I’ve found that perhaps the symptoms may not persistently improve, but patients do tend to feel better. Besides lactose, I think that consuming smaller meals, more frequent meals, and less fatty meals are also helpful for patients.

Recently, many researchers have been interested in both gluten sensitivity and FODMAPS, which stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, and these are essentially a group of carbohydrates in the diet that can cause GI symptoms, particularly diarrhea and bloating.

There is a review on FODMAPS and food intolerances by Barrett and Gibson in the July 2012 issue of Therapeutic Advances in Gastroenterology,³⁹ as well as one from 2011 called Food: The Forgotten Factor by Dr. Eswaran in the Gastroenterology Clinics of North America.⁴⁰ So, I would refer people to those reviews.

Essentially, there seems to be a group of patients who have carbohydrate intolerance. Fructose breath testing can help screen some of those patients, but by no means is it a definitive test for intolerance to carbohydrates.

Gluten is one of those carbohydrates. Essentially, gluten is a fructan, and when people go on a low-FODMAP diet, they inadvertently decrease gluten in their diet, although I think there is a subset of patients who also have sensitivity to wheat that’s different from a food allergy.

So, I think we need to get a better understanding of carbohydrates in the diet because in some patients, they seem to play a role in their symptoms.

DR. CASH: It certainly seems like an easy place to start for our patients as well.

DR. HARRIS: I would urge you to first test patients for celiac disease before you put them on a fructose-restricted diet, because once you reduce gluten in the diet, you may decrease your ability to diagnose celiac disease. I think that is an important consideration, and 10% of patients who have negative celiac disease serology can still have celiac disease even with negative blood tests.⁴¹

DR. CASH: Dr. Chang, it seems like patients and practitioners want to use agents such as probiotics for a myriad of conditions these days. Are there any data that support the use of probiotics in patients with nonconstipation IBS, and, if so, what are the thoughts with regards to how these agents might work?

DR. CHANG: There have actually been a number of studies evaluating the efficacy of probiotics in IBS patients; however, most studies haven’t really focused on a particular bowel habit. There is at least one study where they evaluated IBS with constipation.^42,43

Although there are a number of probiotic studies, most of them are not of high quality. The one probiotic that has been examined in high-quality studies—two different studies—was Bifidobacterium infantis, and this probiotic has been shown to reduce IBS symptoms.^44,45

In one study where they evaluated the medication in caplet form, the improvement in symptoms was seen at 4 weeks.⁴⁵

So one take-home message from that study is that you’d want to keep the patient on probiotics for at least a month to determine whether it’s really efficacious.

The other probiotic that has been studied for IBS and bloating and gas-related symptoms is Bifidobacterium lactis or animalis (it has different names), and this probiotic is present in yogurt available in grocery stores. That has been shown to have some efficacy in decreasing IBS symptoms. But there are several other probiotics that have been shown (albeit not in high-quality studies) to have efficacy in IBS.

There are a number of mechanisms of action that probiotics can help for both digestive health and GI disease, and these include modulating the signals in the gut and affecting immune modulation. By ingesting these probiotics, you may change the composition of the bacterial flora in the gut, which can yield beneficial effects.

There’s also evidence that probiotics maintain the barrier function of the intestinal lining that might be beneficial in IBS, because there is some evidence that IBS patients—or at least a subgroup of IBS patients—have increased intestinal permeability, which may play a role in symptom presentation.

DR. CASH: Dr. Lacy, what medications have evidence to support their use in nonconstipation IBS, and is there a tiered approach to their use?

DR. LACY: I think a good approach is to remind ourselves that we can’t cure IBS, and that our goal is to improve patients’ symptoms. With that in mind, when I see nonconstipated IBS patients, often, I start treatment with an antidiarrheal agent, which might include Imodium or Lomotil. These may improve diarrhea, but they won’t help pain or bloating, which are the most common reasons patients come to see a gastroenterologist.

I frequently use alosetron. This is the only Food and Drug Administration (FDA)-approved medication for women with IBS and diarrhea symptoms. It’s been shown to be safe and effective. I may use a bile acid-binding agent such as cholestyramine or colestipol or colesevelam, although there are very limited data to support their use. It doesn’t mean they don’t work; we just don’t have a lot of data on them.

There are limited data showing that smooth muscle anti-spasmodics, mostly due to their anticholinergic activity, may slow down the action of the GI tract and improve symptoms of pain. Some providers use low-dose tricyclic antidepressants to both slow the GI tract and improve pain. There are also limited data on clonidine and a small study evaluating the use of dextofisopam.

But that’s our armamentarium right now, and I think the art of this job is to try to find the right medication for the right patient while minimizing the side effects.

DR. CASH: Along those lines, Dr. Lacy, there were recently some data with regard to antibiotics for nonconstipation IBS and bloating. Can you describe the relevant data?

DR. LACY: This is a very exciting field, although I think the first thing we need to do is educate both patients and physicians that when we talk about antibiotics, we have to be very careful about how we frame the discussion, ie, we really need to focus on nonabsorbable antibiotics that remain in the GI tract. One of my concerns is that unless you know the area well, or unless you know the data well, you may randomly prescribe a number of different antibiotics for IBS, and this is not only potentially dangerous, but also unhelpful.

When I think about this topic, I think about the broad-spectrum antibiotic rifaximin, which is a nonabsorbable antibiotic that stays within the GI tract and focuses on typical gut bacteria, including gram-negative rods and anaerobic bacteria.

At present, there have been 5 randomized, double-blind, placebo-controlled studies looking at the effects of rifaximin in patients with nonconstipated IBS.^46,47 In summary, these studies together include more than 2000 patients, and it’s been shown that rifaximin has improved not only global symptoms of IBS, but also individual symptoms of bloating, pain, discomfort, and diarrhea. Although it is not FDA-approved—and that is important to mention right now—there are ongoing studies that hopefully will lead to its approval.

If rifaximin isn’t available to your patient, another alternative would be neomycin. There is one small study⁴⁸ showing that neomycin may be effective in IBS patients, but I am just mentioning it because it’s another nonabsorbable antibiotic that I think is safe and at least pathophysiologically makes sense.

DR. CASH: Dr. Harris, any thoughts regarding the use of complementary and alternative medicine for nonconstipation IBS?

DR. HARRIS: As we talk about that, I think we also need to mention some other basic concepts that I discuss with patients, and that is the benefit of exercise and sleep. There have been studies^49,50 that have shown that when patients who have IBS don’t sleep well, they actually may have more pain the following day. So, I always try to emphasize on those important basic health concepts with my patients with IBS.

Additionally, there was one study last year that showed that exercise seems to improve abdominal pain as well in patients with IBS.⁵¹

As for complementary and alternative medicine, there are certain herbal medications, particularly peppermint oil, that can be used. There have been some small trials⁵² that have shown that peppermint oils works as a smooth muscle relaxant, although it’s best if it is in a form that gets digested further down the GI tract in the small bowel—so an encapsulated formulation is more useful—because otherwise, it can increase symptoms of gastroesophageal reflux disease.

Some patients find fennel tea and chamomile soothing, but there are no studies on their efficacy. There was one study that Bensoussan⁵³ did a number of years ago that looked at Chinese herbal medicine, and I don’t know the components of the medicine, but the study did suggest that it had some benefit.

Lastly, these are not complementary therapies necessarily, but to address the mind-body connection of IBS patients, studies have shown that modalities such as mindfulness therapy and cognitive-behavioral therapy (CBT) can be helpful. There have also been some studies^54–56 that have shown that using the CBT technique can help decrease the severity of abdominal pain and discomfort.

I believe there are also some studies with hypnotherapy, and Dr. Chang may be able to expand on those a little bit.

DR. CHANG: Those are more traditional behavioral therapies. There is a recent study⁵⁷ showing that mindfulness meditation, which is becoming increasingly popular and used in other chronic illnesses, could be beneficial in reducing IBS symptoms.

There also have been acupuncture studies in IBS. If you look at uncontrolled studies, it seems that IBS is efficacious, but if you examine controlled studies with either sham acupuncture such as using needles that actually don’t penetrate deeply, the data are less robust and don’t really show much of a significant effect of IBS symptoms.⁵⁸ The augmented interaction between the healthcare provider and patient is the beneficial component of these acupuncture therapy sessions.

DR. CASH: Dr. Chang, as a follow-up to that, what new and emerging therapeutics for IBS with constipation should we be looking toward in the next couple of years?

DR. CHANG: Well, there are 2 therapies that are currently being studied in either a phase II or phase III study. There’s an ongoing phase III study evaluating the efficacy of a kappa opioid receptor agonist, asimadoline, in relieving symptoms in patients with IBS with diarrhea. Asimadoline activates kappa opioid receptors, which are thought to become upregulated or increased in a sensitized chronic pain state such as in patients with particularly more severe symptoms.

A previous phase II study⁵⁹ showed that asimadoline had particular efficacy in the IBS with diarrhea subgroup of patients who had more moderate pain. This is now being currently studied in a larger phase III trial.

There’s also an ongoing phase II trial with a tryptophan hydroxylase 1 inhibitor. This agent decreases the GI levels of serotonin. Basically, it works peripherally. There was a phase II trial where the higher dose of a tryptophan hydroxylase 1 inhibitor helped to decrease overall IBS symptoms and improve stool consistency in IBS with diarrhea.⁶⁰

DR. LACY: There are 2 things I like to ask my patients as I finish the interview and examination: “What are you worried about? What are your fears and concerns?” And I try to address their concerns because data from our laboratory⁶¹ and from Dr. Chang’s laboratory⁶² showed that about 30% of patients are worried that their symptoms represent cancer, and I think it’s a good time to educate and reassure our patients about this.

The second thing I always ask is, “What are your goals.” I think we all see a lot of IBS patients each week, but it continues to strike me that everybody’s goals are very different, and some patients want to focus on just pain, some on just bloating, and some on altered bowel habits. So I’ve given up guessing what their goals are, and I just ask them point blank.

I think that’s very, very useful, and that lets a patient know that, once again, you’re focusing on them. It empowers them to choose the next step—whether they want to choose diet or medications and/or what type of medication.

DR. HARRIS: I would agree totally with Dr. Lacy’s excellent point. I do ask the patient, “What do you want to accomplish when you come to see me? What is your motivation for coming to see me? What problems or symptoms seem to be the most important to you?”

DR. CHANG: I agree with Dr. Lacy and Dr. Harris’s comments, and I would say that many patients, particularly in the clinic population, may have comorbid psychological symptoms, and some of the concerns and fears that were mentioned previously.

I think it’s important for healthcare providers to acknowledge that there may be an influence of the psychological symptoms on their disease or their symptoms, but they need not necessarily feel compelled to cure or fix them. I think that acknowledgment is helpful for patients and that reassurance and some education would be useful.

DR. CASH: I want to thank you all for taking the time to discuss this topic. It’s been very informative and a real pleasure.

FoxP2 Media LLC is the publisher of The Medical Roundtable.

DR. LACY: Let’s tackle the easy one first, and I think that’s the role of colonoscopy. Several studies have pointed out that if patients meet Rome III criteria in the absence of warning signs, the utility of a colonoscopy would be very, very low.

We all agree that if the patient is older than 50 years, and ≥45 years for African Americans, even if there are signs of IBS and you’re pretty confident about the diagnosis, a colonoscopy is still required for screening purposes.

The utility of a colonoscopy in a younger patient—younger than 45 years—with classic symptoms of IBS in the absence of warning signs is extremely low, and I don’t generally recommend that.

One caveat, of course, is that as clinicians, we’re always double-checking to make sure that our diagnosis is correct. We review the patient, see them in follow-up, and make sure that our treatments are appropriate in helping the patients. But if things aren’t making sense, and if the patients aren’t responding, we’ll always go back and question whether the diagnosis was correct, realizing that in some patients with nonconstipated IBS, what appears to be IBS might actually be microscopic colitis, including lymphocytic colitis or collagenous colitis, and celiac disease.

That’s a nice segue, and I think testing for celiac disease is really quite controversial. We know from the study published in Lancet in 2001 by Sanders and colleagues²⁶ that patients with IBS were apparently 5 to 10 times more likely to have celiac disease than those who did not have the disease, and there was a real level of enthusiasm to test nearly all patients with IBS to look for celiac disease.

We also know from the American College of Gastroenterology (ACG) guidelines²⁷ published in 2009 that for patients with diarrhea-predominant IBS or mixed IBS, meaning the nonconstipated IBS patterns, testing for celiac disease is recommended. Keep in mind, of course, that the prevalence in the United States is estimated at about 1%. That being said, I think the best recent investigations were the multicenter trials involving Bethesda Naval and Michigan.²⁸ This multicenter trial involved nearly 500 patients with nonconstipated IBS and nearly the same number of healthy controls who were admitted for routine colonoscopies, and the prevalence of celiac disease was virtually identical. It was 0.41% for IBS patients and 0.44% for controls. Thus, I don’t routinely recommend testing for celiac disease, although if someone has nonconstipated IBS symptoms and they don’t respond to what I think is appropriate initial empiric therapy, at some point, I may check them.

DR. CASH: So, Drs. Harris and Chang, what’s your take on the celiac question and should we be testing for celiac disease in patients with symptoms consistent with nonconstipation IBS?

DR. HARRIS: I find that in patients in whom bloating is a disproportionate symptom, it might be worthwhile to check for celiac disease and review the family history. I think we’ll get into this discussion a little more detail when we discuss the diet, but we also have to think about gluten sensitivity. It’s become more challenging to sort out who truly has celiac disease and who may have gluten sensitivity, and I think those are important considerations.

DR. CHANG: I agree. At this point, the evidence suggests that we should still screen for celiac disease because it is cost effective, since the treatment is so different from that for IBS.

I think for microscopic colitis as well, it would be nice to do a similar cost analysis to determine whether we should be screening for it more than we do because it’s actually fairly prevalent in the population of IBS patients with diarrhea, particularly in middle-aged women, as Brooks’ study demonstrated.²⁹

DR. HARRIS: The prevalence in the Western world is estimated to be 1 in 132 patients.³⁰

That’s a fairly common occurrence for a disorder, so I think the jury is still out. A study previously suggested that celiac disease is more common in IBS patients, and one study suggested that it isn’t so.^27,28,31–33 I think that that the decision to screen or not to screen is not clear yet.

DR. CASH: Yes, it’s still a very controversial issue. Dr. Chang, once the diagnosis has been made, what is the natural history of nonconstipation IBS in terms of surgery rates or the change in diagnosis, perhaps even the risk of developing other disease, which seems to be a common concern of our patients?

DR. CHANG: There was one study that evaluated the natural history of IBS many years ago.³⁴ It reviewed multiple other studies where they followed patients from 6 months to 6 years after the original IBS diagnosis, and they found—consistent with the data that you and others have presented—that the prevalence of determining an alternative diagnosis to IBS is very small.³⁵ It’s about 2% or slightly more than that.

Up to 50% of patients will actually have unchanged symptoms over the years. About 2% to 18% will have worse symptoms.³⁴

If you follow-up the IBS symptoms over time, about a quarter to a third of patients will actually become symptom-free. And we know from post-infectious IBS longitudinal data that the prevalence of IBS declines over time.

In general—and this is something that I tell my patients—the symptoms usually fluctuate over time and much of what we do to treat or manage the symptoms can help to alleviate them to a certain extent. But even when the patients are working hard to manage their symptoms, they can still have symptom flares, although they may be less frequent or milder, and that’s just part of the natural history.

For the bowel habit subtypes, studies have shown that if you follow-up patients, over time, their subtype of IBS can actually change. One study by Doug Drossman and colleagues³⁶ followed IBS patients for over 1 year. They evaluated the symptoms every 3 months in that 1 year and found that 75% of IBS patients actually had a change in their bowel habit subtype over the 1 year.

You would typically see the IBS constipation and the mixed IBS interchanging from one another, and the mixed IBS would also interchange with the IBS with diarrhea. It was less frequent for an IBS with diarrhea to change into an IBS with constipation.

DR. CASH: Certainly, the changing clinical picture of IBS is going to make the evaluation and management of those patients more challenging as well.

Let’s shift over to the topic of treatment. Dr. Harris, you mentioned a few moments ago the role of gluten and perhaps gluten sensitivity. So what role, if any, does diet play in the treatment of nonconstipation IBS?

DR. HARRIS: I think that diet is probably the forgotten factor. Patients have, for years, been telling us that when they eat certain foods, they seem to experience more severe symptoms. They tell us that onions, garlic, fatty, and richer meals cause the symptoms to appear. In fact, Albena Halpert did a study³⁷ that looked at factors in diet that have helped patients, and patients reported that if they ate smaller or less fatty meals or avoid lactose, their IBS symptoms improved.

So, lactose intolerance is a fairly common symptom in the population, in general, and the 2009 ACG guidelines quote a study that showed that the prevalence in the population is about 25%, whereas in the IBS patient population, it’s somewhat higher, around 35% to 38%.³⁸

Patients find that when they avoid lactose, sometimes, there is an improvement in their symptoms of bloating and diarrhea.

In practice, I’ve found that perhaps the symptoms may not persistently improve, but patients do tend to feel better. Besides lactose, I think that consuming smaller meals, more frequent meals, and less fatty meals are also helpful for patients.

Recently, many researchers have been interested in both gluten sensitivity and FODMAPS, which stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, and these are essentially a group of carbohydrates in the diet that can cause GI symptoms, particularly diarrhea and bloating.

There is a review on FODMAPS and food intolerances by Barrett and Gibson in the July 2012 issue of Therapeutic Advances in Gastroenterology,³⁹ as well as one from 2011 called Food: The Forgotten Factor by Dr. Eswaran in the Gastroenterology Clinics of North America.⁴⁰ So, I would refer people to those reviews.

Essentially, there seems to be a group of patients who have carbohydrate intolerance. Fructose breath testing can help screen some of those patients, but by no means is it a definitive test for intolerance to carbohydrates.

Gluten is one of those carbohydrates. Essentially, gluten is a fructan, and when people go on a low-FODMAP diet, they inadvertently decrease gluten in their diet, although I think there is a subset of patients who also have sensitivity to wheat that’s different from a food allergy.

So, I think we need to get a better understanding of carbohydrates in the diet because in some patients, they seem to play a role in their symptoms.

DR. CASH: It certainly seems like an easy place to start for our patients as well.

DR. HARRIS: I would urge you to first test patients for celiac disease before you put them on a fructose-restricted diet, because once you reduce gluten in the diet, you may decrease your ability to diagnose celiac disease. I think that is an important consideration, and 10% of patients who have negative celiac disease serology can still have celiac disease even with negative blood tests.⁴¹

DR. CASH: Dr. Chang, it seems like patients and practitioners want to use agents such as probiotics for a myriad of conditions these days. Are there any data that support the use of probiotics in patients with nonconstipation IBS, and, if so, what are the thoughts with regards to how these agents might work?

DR. CHANG: There have actually been a number of studies evaluating the efficacy of probiotics in IBS patients; however, most studies haven’t really focused on a particular bowel habit. There is at least one study where they evaluated IBS with constipation.^42,43

Although there are a number of probiotic studies, most of them are not of high quality. The one probiotic that has been examined in high-quality studies—two different studies—was Bifidobacterium infantis, and this probiotic has been shown to reduce IBS symptoms.^44,45

In one study where they evaluated the medication in caplet form, the improvement in symptoms was seen at 4 weeks.⁴⁵

So one take-home message from that study is that you’d want to keep the patient on probiotics for at least a month to determine whether it’s really efficacious.

The other probiotic that has been studied for IBS and bloating and gas-related symptoms is Bifidobacterium lactis or animalis (it has different names), and this probiotic is present in yogurt available in grocery stores. That has been shown to have some efficacy in decreasing IBS symptoms. But there are several other probiotics that have been shown (albeit not in high-quality studies) to have efficacy in IBS.

There are a number of mechanisms of action that probiotics can help for both digestive health and GI disease, and these include modulating the signals in the gut and affecting immune modulation. By ingesting these probiotics, you may change the composition of the bacterial flora in the gut, which can yield beneficial effects.

There’s also evidence that probiotics maintain the barrier function of the intestinal lining that might be beneficial in IBS, because there is some evidence that IBS patients—or at least a subgroup of IBS patients—have increased intestinal permeability, which may play a role in symptom presentation.

DR. CASH: Dr. Lacy, what medications have evidence to support their use in nonconstipation IBS, and is there a tiered approach to their use?

DR. LACY: I think a good approach is to remind ourselves that we can’t cure IBS, and that our goal is to improve patients’ symptoms. With that in mind, when I see nonconstipated IBS patients, often, I start treatment with an antidiarrheal agent, which might include Imodium or Lomotil. These may improve diarrhea, but they won’t help pain or bloating, which are the most common reasons patients come to see a gastroenterologist.

I frequently use alosetron. This is the only Food and Drug Administration (FDA)-approved medication for women with IBS and diarrhea symptoms. It’s been shown to be safe and effective. I may use a bile acid-binding agent such as cholestyramine or colestipol or colesevelam, although there are very limited data to support their use. It doesn’t mean they don’t work; we just don’t have a lot of data on them.

There are limited data showing that smooth muscle anti-spasmodics, mostly due to their anticholinergic activity, may slow down the action of the GI tract and improve symptoms of pain. Some providers use low-dose tricyclic antidepressants to both slow the GI tract and improve pain. There are also limited data on clonidine and a small study evaluating the use of dextofisopam.

But that’s our armamentarium right now, and I think the art of this job is to try to find the right medication for the right patient while minimizing the side effects.

DR. CASH: Along those lines, Dr. Lacy, there were recently some data with regard to antibiotics for nonconstipation IBS and bloating. Can you describe the relevant data?

DR. LACY: This is a very exciting field, although I think the first thing we need to do is educate both patients and physicians that when we talk about antibiotics, we have to be very careful about how we frame the discussion, ie, we really need to focus on nonabsorbable antibiotics that remain in the GI tract. One of my concerns is that unless you know the area well, or unless you know the data well, you may randomly prescribe a number of different antibiotics for IBS, and this is not only potentially dangerous, but also unhelpful.

When I think about this topic, I think about the broad-spectrum antibiotic rifaximin, which is a nonabsorbable antibiotic that stays within the GI tract and focuses on typical gut bacteria, including gram-negative rods and anaerobic bacteria.

At present, there have been 5 randomized, double-blind, placebo-controlled studies looking at the effects of rifaximin in patients with nonconstipated IBS.^46,47 In summary, these studies together include more than 2000 patients, and it’s been shown that rifaximin has improved not only global symptoms of IBS, but also individual symptoms of bloating, pain, discomfort, and diarrhea. Although it is not FDA-approved—and that is important to mention right now—there are ongoing studies that hopefully will lead to its approval.

If rifaximin isn’t available to your patient, another alternative would be neomycin. There is one small study⁴⁸ showing that neomycin may be effective in IBS patients, but I am just mentioning it because it’s another nonabsorbable antibiotic that I think is safe and at least pathophysiologically makes sense.

DR. CASH: Dr. Harris, any thoughts regarding the use of complementary and alternative medicine for nonconstipation IBS?

DR. HARRIS: As we talk about that, I think we also need to mention some other basic concepts that I discuss with patients, and that is the benefit of exercise and sleep. There have been studies^49,50 that have shown that when patients who have IBS don’t sleep well, they actually may have more pain the following day. So, I always try to emphasize on those important basic health concepts with my patients with IBS.

Additionally, there was one study last year that showed that exercise seems to improve abdominal pain as well in patients with IBS.⁵¹

As for complementary and alternative medicine, there are certain herbal medications, particularly peppermint oil, that can be used. There have been some small trials⁵² that have shown that peppermint oils works as a smooth muscle relaxant, although it’s best if it is in a form that gets digested further down the GI tract in the small bowel—so an encapsulated formulation is more useful—because otherwise, it can increase symptoms of gastroesophageal reflux disease.

Some patients find fennel tea and chamomile soothing, but there are no studies on their efficacy. There was one study that Bensoussan⁵³ did a number of years ago that looked at Chinese herbal medicine, and I don’t know the components of the medicine, but the study did suggest that it had some benefit.

Lastly, these are not complementary therapies necessarily, but to address the mind-body connection of IBS patients, studies have shown that modalities such as mindfulness therapy and cognitive-behavioral therapy (CBT) can be helpful. There have also been some studies^54–56 that have shown that using the CBT technique can help decrease the severity of abdominal pain and discomfort.

I believe there are also some studies with hypnotherapy, and Dr. Chang may be able to expand on those a little bit.

DR. CHANG: Those are more traditional behavioral therapies. There is a recent study⁵⁷ showing that mindfulness meditation, which is becoming increasingly popular and used in other chronic illnesses, could be beneficial in reducing IBS symptoms.

There also have been acupuncture studies in IBS. If you look at uncontrolled studies, it seems that IBS is efficacious, but if you examine controlled studies with either sham acupuncture such as using needles that actually don’t penetrate deeply, the data are less robust and don’t really show much of a significant effect of IBS symptoms.⁵⁸ The augmented interaction between the healthcare provider and patient is the beneficial component of these acupuncture therapy sessions.

DR. CASH: Dr. Chang, as a follow-up to that, what new and emerging therapeutics for IBS with constipation should we be looking toward in the next couple of years?

DR. CHANG: Well, there are 2 therapies that are currently being studied in either a phase II or phase III study. There’s an ongoing phase III study evaluating the efficacy of a kappa opioid receptor agonist, asimadoline, in relieving symptoms in patients with IBS with diarrhea. Asimadoline activates kappa opioid receptors, which are thought to become upregulated or increased in a sensitized chronic pain state such as in patients with particularly more severe symptoms.

A previous phase II study⁵⁹ showed that asimadoline had particular efficacy in the IBS with diarrhea subgroup of patients who had more moderate pain. This is now being currently studied in a larger phase III trial.

There’s also an ongoing phase II trial with a tryptophan hydroxylase 1 inhibitor. This agent decreases the GI levels of serotonin. Basically, it works peripherally. There was a phase II trial where the higher dose of a tryptophan hydroxylase 1 inhibitor helped to decrease overall IBS symptoms and improve stool consistency in IBS with diarrhea.⁶⁰

DR. LACY: There are 2 things I like to ask my patients as I finish the interview and examination: “What are you worried about? What are your fears and concerns?” And I try to address their concerns because data from our laboratory⁶¹ and from Dr. Chang’s laboratory⁶² showed that about 30% of patients are worried that their symptoms represent cancer, and I think it’s a good time to educate and reassure our patients about this.

The second thing I always ask is, “What are your goals.” I think we all see a lot of IBS patients each week, but it continues to strike me that everybody’s goals are very different, and some patients want to focus on just pain, some on just bloating, and some on altered bowel habits. So I’ve given up guessing what their goals are, and I just ask them point blank.

I think that’s very, very useful, and that lets a patient know that, once again, you’re focusing on them. It empowers them to choose the next step—whether they want to choose diet or medications and/or what type of medication.

DR. HARRIS: I would agree totally with Dr. Lacy’s excellent point. I do ask the patient, “What do you want to accomplish when you come to see me? What is your motivation for coming to see me? What problems or symptoms seem to be the most important to you?”

DR. CHANG: I agree with Dr. Lacy and Dr. Harris’s comments, and I would say that many patients, particularly in the clinic population, may have comorbid psychological symptoms, and some of the concerns and fears that were mentioned previously.

I think it’s important for healthcare providers to acknowledge that there may be an influence of the psychological symptoms on their disease or their symptoms, but they need not necessarily feel compelled to cure or fix them. I think that acknowledgment is helpful for patients and that reassurance and some education would be useful.

DR. CASH: I want to thank you all for taking the time to discuss this topic. It’s been very informative and a real pleasure.

FoxP2 Media LLC is the publisher of The Medical Roundtable.

DR. LACY: Let’s tackle the easy one first, and I think that’s the role of colonoscopy. Several studies have pointed out that if patients meet Rome III criteria in the absence of warning signs, the utility of a colonoscopy would be very, very low.

We all agree that if the patient is older than 50 years, and ≥45 years for African Americans, even if there are signs of IBS and you’re pretty confident about the diagnosis, a colonoscopy is still required for screening purposes.

The utility of a colonoscopy in a younger patient—younger than 45 years—with classic symptoms of IBS in the absence of warning signs is extremely low, and I don’t generally recommend that.

One caveat, of course, is that as clinicians, we’re always double-checking to make sure that our diagnosis is correct. We review the patient, see them in follow-up, and make sure that our treatments are appropriate in helping the patients. But if things aren’t making sense, and if the patients aren’t responding, we’ll always go back and question whether the diagnosis was correct, realizing that in some patients with nonconstipated IBS, what appears to be IBS might actually be microscopic colitis, including lymphocytic colitis or collagenous colitis, and celiac disease.

That’s a nice segue, and I think testing for celiac disease is really quite controversial. We know from the study published in Lancet in 2001 by Sanders and colleagues²⁶ that patients with IBS were apparently 5 to 10 times more likely to have celiac disease than those who did not have the disease, and there was a real level of enthusiasm to test nearly all patients with IBS to look for celiac disease.

We also know from the American College of Gastroenterology (ACG) guidelines²⁷ published in 2009 that for patients with diarrhea-predominant IBS or mixed IBS, meaning the nonconstipated IBS patterns, testing for celiac disease is recommended. Keep in mind, of course, that the prevalence in the United States is estimated at about 1%. That being said, I think the best recent investigations were the multicenter trials involving Bethesda Naval and Michigan.²⁸ This multicenter trial involved nearly 500 patients with nonconstipated IBS and nearly the same number of healthy controls who were admitted for routine colonoscopies, and the prevalence of celiac disease was virtually identical. It was 0.41% for IBS patients and 0.44% for controls. Thus, I don’t routinely recommend testing for celiac disease, although if someone has nonconstipated IBS symptoms and they don’t respond to what I think is appropriate initial empiric therapy, at some point, I may check them.

DR. CASH: So, Drs. Harris and Chang, what’s your take on the celiac question and should we be testing for celiac disease in patients with symptoms consistent with nonconstipation IBS?

DR. HARRIS: I find that in patients in whom bloating is a disproportionate symptom, it might be worthwhile to check for celiac disease and review the family history. I think we’ll get into this discussion a little more detail when we discuss the diet, but we also have to think about gluten sensitivity. It’s become more challenging to sort out who truly has celiac disease and who may have gluten sensitivity, and I think those are important considerations.

DR. CHANG: I agree. At this point, the evidence suggests that we should still screen for celiac disease because it is cost effective, since the treatment is so different from that for IBS.

I think for microscopic colitis as well, it would be nice to do a similar cost analysis to determine whether we should be screening for it more than we do because it’s actually fairly prevalent in the population of IBS patients with diarrhea, particularly in middle-aged women, as Brooks’ study demonstrated.²⁹

DR. HARRIS: The prevalence in the Western world is estimated to be 1 in 132 patients.³⁰

That’s a fairly common occurrence for a disorder, so I think the jury is still out. A study previously suggested that celiac disease is more common in IBS patients, and one study suggested that it isn’t so.^27,28,31–33 I think that that the decision to screen or not to screen is not clear yet.

DR. CASH: Yes, it’s still a very controversial issue. Dr. Chang, once the diagnosis has been made, what is the natural history of nonconstipation IBS in terms of surgery rates or the change in diagnosis, perhaps even the risk of developing other disease, which seems to be a common concern of our patients?

DR. CHANG: There was one study that evaluated the natural history of IBS many years ago.³⁴ It reviewed multiple other studies where they followed patients from 6 months to 6 years after the original IBS diagnosis, and they found—consistent with the data that you and others have presented—that the prevalence of determining an alternative diagnosis to IBS is very small.³⁵ It’s about 2% or slightly more than that.

Up to 50% of patients will actually have unchanged symptoms over the years. About 2% to 18% will have worse symptoms.³⁴

If you follow-up the IBS symptoms over time, about a quarter to a third of patients will actually become symptom-free. And we know from post-infectious IBS longitudinal data that the prevalence of IBS declines over time.

In general—and this is something that I tell my patients—the symptoms usually fluctuate over time and much of what we do to treat or manage the symptoms can help to alleviate them to a certain extent. But even when the patients are working hard to manage their symptoms, they can still have symptom flares, although they may be less frequent or milder, and that’s just part of the natural history.

For the bowel habit subtypes, studies have shown that if you follow-up patients, over time, their subtype of IBS can actually change. One study by Doug Drossman and colleagues³⁶ followed IBS patients for over 1 year. They evaluated the symptoms every 3 months in that 1 year and found that 75% of IBS patients actually had a change in their bowel habit subtype over the 1 year.

You would typically see the IBS constipation and the mixed IBS interchanging from one another, and the mixed IBS would also interchange with the IBS with diarrhea. It was less frequent for an IBS with diarrhea to change into an IBS with constipation.

DR. CASH: Certainly, the changing clinical picture of IBS is going to make the evaluation and management of those patients more challenging as well.

Let’s shift over to the topic of treatment. Dr. Harris, you mentioned a few moments ago the role of gluten and perhaps gluten sensitivity. So what role, if any, does diet play in the treatment of nonconstipation IBS?

DR. HARRIS: I think that diet is probably the forgotten factor. Patients have, for years, been telling us that when they eat certain foods, they seem to experience more severe symptoms. They tell us that onions, garlic, fatty, and richer meals cause the symptoms to appear. In fact, Albena Halpert did a study³⁷ that looked at factors in diet that have helped patients, and patients reported that if they ate smaller or less fatty meals or avoid lactose, their IBS symptoms improved.

So, lactose intolerance is a fairly common symptom in the population, in general, and the 2009 ACG guidelines quote a study that showed that the prevalence in the population is about 25%, whereas in the IBS patient population, it’s somewhat higher, around 35% to 38%.³⁸

Patients find that when they avoid lactose, sometimes, there is an improvement in their symptoms of bloating and diarrhea.

In practice, I’ve found that perhaps the symptoms may not persistently improve, but patients do tend to feel better. Besides lactose, I think that consuming smaller meals, more frequent meals, and less fatty meals are also helpful for patients.

Recently, many researchers have been interested in both gluten sensitivity and FODMAPS, which stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, and these are essentially a group of carbohydrates in the diet that can cause GI symptoms, particularly diarrhea and bloating.

There is a review on FODMAPS and food intolerances by Barrett and Gibson in the July 2012 issue of Therapeutic Advances in Gastroenterology,³⁹ as well as one from 2011 called Food: The Forgotten Factor by Dr. Eswaran in the Gastroenterology Clinics of North America.⁴⁰ So, I would refer people to those reviews.

Essentially, there seems to be a group of patients who have carbohydrate intolerance. Fructose breath testing can help screen some of those patients, but by no means is it a definitive test for intolerance to carbohydrates.

Gluten is one of those carbohydrates. Essentially, gluten is a fructan, and when people go on a low-FODMAP diet, they inadvertently decrease gluten in their diet, although I think there is a subset of patients who also have sensitivity to wheat that’s different from a food allergy.

So, I think we need to get a better understanding of carbohydrates in the diet because in some patients, they seem to play a role in their symptoms.

DR. CASH: It certainly seems like an easy place to start for our patients as well.

DR. HARRIS: I would urge you to first test patients for celiac disease before you put them on a fructose-restricted diet, because once you reduce gluten in the diet, you may decrease your ability to diagnose celiac disease. I think that is an important consideration, and 10% of patients who have negative celiac disease serology can still have celiac disease even with negative blood tests.⁴¹

DR. CASH: Dr. Chang, it seems like patients and practitioners want to use agents such as probiotics for a myriad of conditions these days. Are there any data that support the use of probiotics in patients with nonconstipation IBS, and, if so, what are the thoughts with regards to how these agents might work?

DR. CHANG: There have actually been a number of studies evaluating the efficacy of probiotics in IBS patients; however, most studies haven’t really focused on a particular bowel habit. There is at least one study where they evaluated IBS with constipation.^42,43

Although there are a number of probiotic studies, most of them are not of high quality. The one probiotic that has been examined in high-quality studies—two different studies—was Bifidobacterium infantis, and this probiotic has been shown to reduce IBS symptoms.^44,45

In one study where they evaluated the medication in caplet form, the improvement in symptoms was seen at 4 weeks.⁴⁵

So one take-home message from that study is that you’d want to keep the patient on probiotics for at least a month to determine whether it’s really efficacious.

The other probiotic that has been studied for IBS and bloating and gas-related symptoms is Bifidobacterium lactis or animalis (it has different names), and this probiotic is present in yogurt available in grocery stores. That has been shown to have some efficacy in decreasing IBS symptoms. But there are several other probiotics that have been shown (albeit not in high-quality studies) to have efficacy in IBS.

There are a number of mechanisms of action that probiotics can help for both digestive health and GI disease, and these include modulating the signals in the gut and affecting immune modulation. By ingesting these probiotics, you may change the composition of the bacterial flora in the gut, which can yield beneficial effects.

There’s also evidence that probiotics maintain the barrier function of the intestinal lining that might be beneficial in IBS, because there is some evidence that IBS patients—or at least a subgroup of IBS patients—have increased intestinal permeability, which may play a role in symptom presentation.

DR. CASH: Dr. Lacy, what medications have evidence to support their use in nonconstipation IBS, and is there a tiered approach to their use?

DR. LACY: I think a good approach is to remind ourselves that we can’t cure IBS, and that our goal is to improve patients’ symptoms. With that in mind, when I see nonconstipated IBS patients, often, I start treatment with an antidiarrheal agent, which might include Imodium or Lomotil. These may improve diarrhea, but they won’t help pain or bloating, which are the most common reasons patients come to see a gastroenterologist.

I frequently use alosetron. This is the only Food and Drug Administration (FDA)-approved medication for women with IBS and diarrhea symptoms. It’s been shown to be safe and effective. I may use a bile acid-binding agent such as cholestyramine or colestipol or colesevelam, although there are very limited data to support their use. It doesn’t mean they don’t work; we just don’t have a lot of data on them.

There are limited data showing that smooth muscle anti-spasmodics, mostly due to their anticholinergic activity, may slow down the action of the GI tract and improve symptoms of pain. Some providers use low-dose tricyclic antidepressants to both slow the GI tract and improve pain. There are also limited data on clonidine and a small study evaluating the use of dextofisopam.

But that’s our armamentarium right now, and I think the art of this job is to try to find the right medication for the right patient while minimizing the side effects.

DR. CASH: Along those lines, Dr. Lacy, there were recently some data with regard to antibiotics for nonconstipation IBS and bloating. Can you describe the relevant data?

DR. LACY: This is a very exciting field, although I think the first thing we need to do is educate both patients and physicians that when we talk about antibiotics, we have to be very careful about how we frame the discussion, ie, we really need to focus on nonabsorbable antibiotics that remain in the GI tract. One of my concerns is that unless you know the area well, or unless you know the data well, you may randomly prescribe a number of different antibiotics for IBS, and this is not only potentially dangerous, but also unhelpful.

When I think about this topic, I think about the broad-spectrum antibiotic rifaximin, which is a nonabsorbable antibiotic that stays within the GI tract and focuses on typical gut bacteria, including gram-negative rods and anaerobic bacteria.

At present, there have been 5 randomized, double-blind, placebo-controlled studies looking at the effects of rifaximin in patients with nonconstipated IBS.^46,47 In summary, these studies together include more than 2000 patients, and it’s been shown that rifaximin has improved not only global symptoms of IBS, but also individual symptoms of bloating, pain, discomfort, and diarrhea. Although it is not FDA-approved—and that is important to mention right now—there are ongoing studies that hopefully will lead to its approval.

If rifaximin isn’t available to your patient, another alternative would be neomycin. There is one small study⁴⁸ showing that neomycin may be effective in IBS patients, but I am just mentioning it because it’s another nonabsorbable antibiotic that I think is safe and at least pathophysiologically makes sense.

DR. CASH: Dr. Harris, any thoughts regarding the use of complementary and alternative medicine for nonconstipation IBS?

DR. HARRIS: As we talk about that, I think we also need to mention some other basic concepts that I discuss with patients, and that is the benefit of exercise and sleep. There have been studies^49,50 that have shown that when patients who have IBS don’t sleep well, they actually may have more pain the following day. So, I always try to emphasize on those important basic health concepts with my patients with IBS.

Additionally, there was one study last year that showed that exercise seems to improve abdominal pain as well in patients with IBS.⁵¹

As for complementary and alternative medicine, there are certain herbal medications, particularly peppermint oil, that can be used. There have been some small trials⁵² that have shown that peppermint oils works as a smooth muscle relaxant, although it’s best if it is in a form that gets digested further down the GI tract in the small bowel—so an encapsulated formulation is more useful—because otherwise, it can increase symptoms of gastroesophageal reflux disease.

Some patients find fennel tea and chamomile soothing, but there are no studies on their efficacy. There was one study that Bensoussan⁵³ did a number of years ago that looked at Chinese herbal medicine, and I don’t know the components of the medicine, but the study did suggest that it had some benefit.

Lastly, these are not complementary therapies necessarily, but to address the mind-body connection of IBS patients, studies have shown that modalities such as mindfulness therapy and cognitive-behavioral therapy (CBT) can be helpful. There have also been some studies^54–56 that have shown that using the CBT technique can help decrease the severity of abdominal pain and discomfort.

I believe there are also some studies with hypnotherapy, and Dr. Chang may be able to expand on those a little bit.

DR. CHANG: Those are more traditional behavioral therapies. There is a recent study⁵⁷ showing that mindfulness meditation, which is becoming increasingly popular and used in other chronic illnesses, could be beneficial in reducing IBS symptoms.

There also have been acupuncture studies in IBS. If you look at uncontrolled studies, it seems that IBS is efficacious, but if you examine controlled studies with either sham acupuncture such as using needles that actually don’t penetrate deeply, the data are less robust and don’t really show much of a significant effect of IBS symptoms.⁵⁸ The augmented interaction between the healthcare provider and patient is the beneficial component of these acupuncture therapy sessions.

DR. CASH: Dr. Chang, as a follow-up to that, what new and emerging therapeutics for IBS with constipation should we be looking toward in the next couple of years?

DR. CHANG: Well, there are 2 therapies that are currently being studied in either a phase II or phase III study. There’s an ongoing phase III study evaluating the efficacy of a kappa opioid receptor agonist, asimadoline, in relieving symptoms in patients with IBS with diarrhea. Asimadoline activates kappa opioid receptors, which are thought to become upregulated or increased in a sensitized chronic pain state such as in patients with particularly more severe symptoms.

A previous phase II study⁵⁹ showed that asimadoline had particular efficacy in the IBS with diarrhea subgroup of patients who had more moderate pain. This is now being currently studied in a larger phase III trial.

There’s also an ongoing phase II trial with a tryptophan hydroxylase 1 inhibitor. This agent decreases the GI levels of serotonin. Basically, it works peripherally. There was a phase II trial where the higher dose of a tryptophan hydroxylase 1 inhibitor helped to decrease overall IBS symptoms and improve stool consistency in IBS with diarrhea.⁶⁰

DR. LACY: There are 2 things I like to ask my patients as I finish the interview and examination: “What are you worried about? What are your fears and concerns?” And I try to address their concerns because data from our laboratory⁶¹ and from Dr. Chang’s laboratory⁶² showed that about 30% of patients are worried that their symptoms represent cancer, and I think it’s a good time to educate and reassure our patients about this.

The second thing I always ask is, “What are your goals.” I think we all see a lot of IBS patients each week, but it continues to strike me that everybody’s goals are very different, and some patients want to focus on just pain, some on just bloating, and some on altered bowel habits. So I’ve given up guessing what their goals are, and I just ask them point blank.

I think that’s very, very useful, and that lets a patient know that, once again, you’re focusing on them. It empowers them to choose the next step—whether they want to choose diet or medications and/or what type of medication.

DR. HARRIS: I would agree totally with Dr. Lacy’s excellent point. I do ask the patient, “What do you want to accomplish when you come to see me? What is your motivation for coming to see me? What problems or symptoms seem to be the most important to you?”

DR. CHANG: I agree with Dr. Lacy and Dr. Harris’s comments, and I would say that many patients, particularly in the clinic population, may have comorbid psychological symptoms, and some of the concerns and fears that were mentioned previously.

I think it’s important for healthcare providers to acknowledge that there may be an influence of the psychological symptoms on their disease or their symptoms, but they need not necessarily feel compelled to cure or fix them. I think that acknowledgment is helpful for patients and that reassurance and some education would be useful.

DR. CASH: I want to thank you all for taking the time to discuss this topic. It’s been very informative and a real pleasure.

FoxP2 Media LLC is the publisher of The Medical Roundtable.

Regarding consumer access, it is important to find safe gluten-free foods that are not cross-contaminated. We now have a Food Allergen Labeling and Consumer Protection Act in place that states that if wheat protein is in an FDA-regulated food, it must be labeled as such on the package. That applies to FDA foods but not USDA foods. Dieticians know the difference between these two and can educate their patients, but it’s not obvious by just reading a label.

The most obvious sources of gluten are wheat, rye, barley, malt, oats (unless they are specifically labeled and processed such that they are gluten free), and brewer’s yeast. These are easily identifiable, but it takes a little bit of education to get familiar with hidden gluten sources. One of the primary things that a person can do is make sure that their grains and flour-based products are labeled “gluten free” to help avoid some of the risks of cross-contamination that come when gluten-free grains are contaminated with wheat, rye, or barley during the farming, processing, or milling practices that typically occur in this country.

DR. MUSHLIN: So let’s say I’ve got a patient who says to me, “Doc, I’ve got celiac disease. Can I ever eat out again? Can I ever go to a restaurant?” How would you advise them?

MS. DENNIS: I have celiac disease myself, and yes you can absolutely eat out. I was diagnosed 22 years ago. So much has changed in these last 2 decades that makes life a lot easier for us, but you do have to pay attention when dining out, not only to the ingredients that are going into the food but also to the preparation technique used.

If a newly diagnosed person goes out to eat, they would want to first choose a celiac-friendly restaurant, meaning a restaurant that has a gluten-free menu. Even then, I would suggest asking questions related to the ingredients and the preparation methods. For example, it’s pretty common knowledge among people with celiac disease that fryers are contaminated, but what’s less commonly known is that scrambled eggs can often be mixed with pancake batter to make them fluffy and increase their volume. Roasts and beef cuts that are served in a restaurant are often held in a broth that contains wheat, prior to being served. Baked potatoes may be put into a fryer just before serving them at the table.

It’s important that in the kitchen, where the food is being prepared, different utensils and skillets are used, and that the person preparing the food is paying attention to what cutting boards he/she is using and not cross-contaminating with other gluten-containing products. All of this being said, there is much more opportunity for people to dine out these days. However, you have to be very, very careful, and there are resources that can lead you to restaurants that are more inclined to understand food allergies and make allowances and substitutions for those on the gluten-free diet.

DR. MUSHLIN: Ms. Dennis, would you elaborate on how to access those resources, and can you also discuss a few reputable websites that can be used by people with gluten sensitivity?

MS. DENNIS: There are a number of national organizations that are deeply committed to celiac disease, the gluten-free diet, and those with non-celiac gluten sensitivity. In no particular order, these include the Celiac Disease Foundation (www.celiac.org), the Gluten Intolerance Group (www.gluten.net), the Celiac Sprue Association of the United States (CSA/USA, Inc; www.csaceliacs.info), the American Celiac Disease Alliance (americanceliac.org), and the National Foundation for Celiac Awareness (www.celiaccentral.org). These can all be easily found by a Google search. Each of them contains multiple listings of resources including restaurants, information about dining out, tips on how to eat when traveling, nutrition information, hidden gluten sources, blogs, and how to budget on the gluten-free diet. Many of them list celiac centers across the United States and describe how to find specific clinicians who are experts in this field. All of these are reputable sites.

I should mention that we have also launched a multi-level website especially designed for the nutritional management of celiac disease: CeliacNow.org. It’s useful for anyone on the gluten-free diet as well as practitioners who want to gain more information.

Back to your original question about dining out in particular, there are 2 resources that I recommend to patients. One of them is TriumphDining.com. Not only do they list grocery stores and food sources across the state, they also list restaurants. CeceliasMarketplace.com is also another excellent website. Both of these sites also offer books on the topic. Finally, the forum at www.celiac.com is a place that most people find almost immediately when they’re diagnosed.

DR. MUSHLIN: Good. Is there any special designation for people who do nutritional work such as yourself who specialize in celiac counseling, or can any registered nutritionist counsel someone appropriately?

MS. DENNIS: They are actually working on a certification program for the counseling of patients with celiac disease. I joined a taskforce about 5 years ago that developed nutritional guidelines for the Academy of Nutrition and Dietetics.³ These guidelines are available if dieticians want to train themselves on how to counsel a patient on the gluten-free diet, beginning with the initial visit through the follow-up visits. The guidelines include laboratory tests, case studies, and multiple patient handouts, and they constitute the industry’s major educational piece on celiac disease. Beyond that, you can examine books, articles, etc, written by a number of experts in the field. There’s currently no certification.

DR. LEFFLER: A lot of patients will come to me saying, “I saw a dietician and I knew more about the diet than they did. They were no help at all.” That is really a terribly frustrating thing for patients. So, clinicians want to make sure that they send their patients to somebody who has a fair degree of knowledge, interest, and expertise in celiac disease. Unfortunately, this expertise is just not that common these days.

DR. MUSHLIN: Ms. Dennis, how many hours do you normally have to spend to get a newly diagnosed patient with true celiac disease, not just gluten sensitivity, up to speed assuming they have normal intelligence, at least a high school education, and some kind of familiarity with the basics of nutrition. How many hours might it take for you to meet with them? Often when physicians send a patient for a consultation, it’s helpful to tell the patient that they may need to be seen a few times to get it right because sometimes patients are surprised or dismayed that 20minutes with someone hasn’t fixed them.

MS. DENNIS: In this hospital setting, I’m not able to see patients as often or for as long of a period of time as I would like, and that’s common across many, many nutrition practices. We have an hour to educate patients initially. In an ideal world, the patients would be back within a few weeks for part 2 for at least an hour, and then they would check in periodically for the next 3months, 6months, and then yearly for a wellness check.

You can absolutely not do this in one session, and so, I’ve designed nutrition counseling sessions to give patients a tremendous amount of information that they can read. I also instruct them to explore reputable sites, read the material that we’ve created, and then come back with questions. I always link them to a local support group, which is absolutely critical for the management of this lifestyle adjustment. They can’t cope with the condition alone, and they certainly can’t do it on a few hours of nutrition consulting.

DR. MUSHLIN: Are you folks doing group counseling yet at your institution? For example, patients who’ve spent an hour or greater with you can come back in a group setting to get their questions answered, have an open discussion, and obtain support from other fellow patients or from other individuals following the same diet.

MS. DENNIS: Our clinic visits are one-on-one, but we do offer patient education nights 3 times a year where 10 to 40 people join us, and one of the doctors and I sit and answer questions for an hour and a half. That is a great experience for the patients. It’s always a very warm environment, and we again connect them to our larger support group that serves all of New England, the Healthy Villi, and they’re able to attend conferences, expos, or large meetings at least 3 times a year.

DR. MUSHLIN: I certainly think that if the paradigms of helping patients with chronic ongoing illness can be managed, their illnesses are going to gravitate more and more toward exactly those kinds of group support models.

MS. DENNIS: I agree.

DR. MUSHLIN: Dr. Leffler, you’ve mentioned briefly that in follow-up with your patients who have celiac disease, you need to be careful or be aware of the possibility of low bone density, and you also mentioned that they need vaccinations. What vaccinations do they require and why?

DR. LEFFLER: One of the things that is not widely known about celiac disease is that it’s actually associated with functional hyposplenism. So, people with celiac disease have an increased risk of infections—primarily those involving encapsulated organisms but also other infections—and these infections can be more severe. Our general recommendations are to vaccinate all celiac patients for flu and pneumococcus regardless of their age. Unfortunately, we have seen cases of very severe pneumococcal sepsis in otherwise totally healthy immunocompetent patients with celiac disease. So, it is something that we recommend routinely to all of our patients.

DR. MUSHLIN: Regarding the unusual association of celiac disease with other medical situations, one of my colleagues here saw a patient with pulmonary hemosiderosis who happened to have celiac disease. Are there other unusual conditions that are associated with celiac disease?

DR. LEFFLER: Yes. That pulmonary condition is called Lane-Hamilton syndrome. It is quite rare, but we’ve seen a few cases of it.

One of the fascinating things about celiac disease is that it can affect any organ system in the body. You can see effects in the central nervous system, skin, bones, kidneys, reproductive system, lungs, and heart, and there are a number of reasons why celiac disease can be so far-reaching.

Part of it is just that chronic nutritional deficiencies can lead to widespread problems, but more fundamentally, people with celiac disease produce antibodies to tTG. That’s the blood test that is most commonly ordered—the IgA anti-tTG blood test. The enzyme tTG is found in all parts of the body. Its main job is to crosslink collagen. It’s very active in wound repair and building connective tissue, and when antibodies attack this enzyme, inflammation can occur anywhere in the body. Presumably, depending on the exact type of antibodies produced and polymorphisms in tTGs, you can have a direct autoimmune effect that’s triggered in the intestine but attacks the brain or virtually any other organ.

Gluten ataxia is a cardinal well-known phenomenon where you have cerebellar inflammation and cerebellar atrophy due to the celiac reaction. You can have dermatitis herpetiformis, which is an inflammatory reaction of the skin that mostly affects extensor surfaces. So, you have this autoimmune reaction that can attack any part of the body but starts in the intestine. Once you get celiac disease under control, for example by going on a gluten-free diet, these antibody levels decrease and the autoimmune reactions cease just as they do in the intestine. This is really a very unique way of thinking about an autoimmune disease.

DR. MUSHLIN: Because we’re talking so much about antibodies, do you follow antibody titers in people you’ve placed on a gluten-free diet?

DR. LEFFLER: Yes, I do. I follow them not because they’re really wonderful at monitoring celiac disease, because they’re not. There is plenty of research including some that we’ve done ourselves^4,5 that shows that they’re not great at telling, for instance, recent gluten exposure or the degree of intestinal healing. There are lots of people who have completely normal antibody levels, but their intestine’s ability to heal is significantly damaged and vice versa. Some people still have mild elevations in their antibody levels, but their intestine looks pretty good.

On the other hand, there’s really no other tool that we have, and if you have somebody with antibody levels that are persistently elevated and never drop, or drop slightly but are still 2 to 3 times the upper limit of normal, you can be fairly certain that gluten is sneaking in somewhere, and they may not know it. They may be doing their best to follow a gluten-free diet. It could be something as simple as a single generic medication or a supplement that has gluten in it that they’re taking on a daily basis. We’ve seen issues of that sort, but if their antibody level is still high, it’s very helpful as a red flag that something’s not going right.

The first thing I’ll do is send them back to see Ms. Dennis to review the diet and see where the problems are cropping up. That will fix many of the problems, but it can take an awful lot of detective work to sort through basically everything that they’re putting in their mouth and see where that bit of gluten might be.

DR. MUSHLIN: So let’s say the family practitioner diagnoses celiac disease based on the patient’s history and physical findings, and the tTG antibody test is highly positive. The practitioner then sends the patient to a nutritionist, and the patient goes on a gluten-free diet. How should that family practitioner then follow up with the patient? You mentioned immunizations—influenza yearly and Pneumovax. What else should be routinely done by that practitioner, for example, in a rural community where the patient might not have access to a specialist?

DR. LEFFLER: I want to just mention that even with a positive antibody level, endoscopy is still necessary at the beginning for diagnosis. The standard of care for celiac disease these days includes checking celiac serologies approximately every 3 to 6months until they normalize, which depends on how high they are at the beginning. Some people start off with a relative titer of 1000, and some start off with a relative titer of 50. Obviously, the latter will normalize much more quickly.

What you want to see is an improvement in those levels, so you follow them approximately every 6months until they normalize. Then you perform a celiac blood test approximately every year just to make sure that the levels are staying low and that something hasn’t changed such that the patient suddenly has an elevated level. At least 1 bone mineral density test should be performed approximately 1 year after diagnosis once their vitamin D and any other nutritional deficiencies have been repleted. We can mention the nutrients to check in a second, and if those are normal, then the patient can go back to the bone mineral density recommendations for the regular population.

If their bone mineral density is low, then you want to keep a closer eye on them depending on how low it is. You can see a lot of improvement in bone mineral density in the first year after diagnosis with celiac disease, which is why we don’t typically check bone density right off the bat unless the patient has had fractures or something that we’re really worried about. It’s only the residual osteopenia or osteoporosis that they have after a year that we would treat differently.

Even after the initial dietary counseling, we strongly recommend that patients check in with their dietician once a year. Again, a gluten-free diet is a really big change. It’s tough. Things change all the time, and by following up with a specialist, you can tell them about how the foods you eat have changed. New recommendations on a yearly basis are also recommended.

As for vitamins, the most common nutrient deficiencies in people with celiac disease are currently vitamin D, iron, and zinc. Zinc is not one that’s commonly on people’s radar, but it is actually responsible for a lot of the hair and skin manifestations that people with celiac disease complain about and potentially responsible for some of the immune dysregulation as well.

Regarding consumer access, it is important to find safe gluten-free foods that are not cross-contaminated. We now have a Food Allergen Labeling and Consumer Protection Act in place that states that if wheat protein is in an FDA-regulated food, it must be labeled as such on the package. That applies to FDA foods but not USDA foods. Dieticians know the difference between these two and can educate their patients, but it’s not obvious by just reading a label.

The most obvious sources of gluten are wheat, rye, barley, malt, oats (unless they are specifically labeled and processed such that they are gluten free), and brewer’s yeast. These are easily identifiable, but it takes a little bit of education to get familiar with hidden gluten sources. One of the primary things that a person can do is make sure that their grains and flour-based products are labeled “gluten free” to help avoid some of the risks of cross-contamination that come when gluten-free grains are contaminated with wheat, rye, or barley during the farming, processing, or milling practices that typically occur in this country.

DR. MUSHLIN: So let’s say I’ve got a patient who says to me, “Doc, I’ve got celiac disease. Can I ever eat out again? Can I ever go to a restaurant?” How would you advise them?

MS. DENNIS: I have celiac disease myself, and yes you can absolutely eat out. I was diagnosed 22 years ago. So much has changed in these last 2 decades that makes life a lot easier for us, but you do have to pay attention when dining out, not only to the ingredients that are going into the food but also to the preparation technique used.

If a newly diagnosed person goes out to eat, they would want to first choose a celiac-friendly restaurant, meaning a restaurant that has a gluten-free menu. Even then, I would suggest asking questions related to the ingredients and the preparation methods. For example, it’s pretty common knowledge among people with celiac disease that fryers are contaminated, but what’s less commonly known is that scrambled eggs can often be mixed with pancake batter to make them fluffy and increase their volume. Roasts and beef cuts that are served in a restaurant are often held in a broth that contains wheat, prior to being served. Baked potatoes may be put into a fryer just before serving them at the table.

It’s important that in the kitchen, where the food is being prepared, different utensils and skillets are used, and that the person preparing the food is paying attention to what cutting boards he/she is using and not cross-contaminating with other gluten-containing products. All of this being said, there is much more opportunity for people to dine out these days. However, you have to be very, very careful, and there are resources that can lead you to restaurants that are more inclined to understand food allergies and make allowances and substitutions for those on the gluten-free diet.

DR. MUSHLIN: Ms. Dennis, would you elaborate on how to access those resources, and can you also discuss a few reputable websites that can be used by people with gluten sensitivity?

MS. DENNIS: There are a number of national organizations that are deeply committed to celiac disease, the gluten-free diet, and those with non-celiac gluten sensitivity. In no particular order, these include the Celiac Disease Foundation (www.celiac.org), the Gluten Intolerance Group (www.gluten.net), the Celiac Sprue Association of the United States (CSA/USA, Inc; www.csaceliacs.info), the American Celiac Disease Alliance (americanceliac.org), and the National Foundation for Celiac Awareness (www.celiaccentral.org). These can all be easily found by a Google search. Each of them contains multiple listings of resources including restaurants, information about dining out, tips on how to eat when traveling, nutrition information, hidden gluten sources, blogs, and how to budget on the gluten-free diet. Many of them list celiac centers across the United States and describe how to find specific clinicians who are experts in this field. All of these are reputable sites.

I should mention that we have also launched a multi-level website especially designed for the nutritional management of celiac disease: CeliacNow.org. It’s useful for anyone on the gluten-free diet as well as practitioners who want to gain more information.

Back to your original question about dining out in particular, there are 2 resources that I recommend to patients. One of them is TriumphDining.com. Not only do they list grocery stores and food sources across the state, they also list restaurants. CeceliasMarketplace.com is also another excellent website. Both of these sites also offer books on the topic. Finally, the forum at www.celiac.com is a place that most people find almost immediately when they’re diagnosed.

DR. MUSHLIN: Good. Is there any special designation for people who do nutritional work such as yourself who specialize in celiac counseling, or can any registered nutritionist counsel someone appropriately?

MS. DENNIS: They are actually working on a certification program for the counseling of patients with celiac disease. I joined a taskforce about 5 years ago that developed nutritional guidelines for the Academy of Nutrition and Dietetics.³ These guidelines are available if dieticians want to train themselves on how to counsel a patient on the gluten-free diet, beginning with the initial visit through the follow-up visits. The guidelines include laboratory tests, case studies, and multiple patient handouts, and they constitute the industry’s major educational piece on celiac disease. Beyond that, you can examine books, articles, etc, written by a number of experts in the field. There’s currently no certification.

DR. LEFFLER: A lot of patients will come to me saying, “I saw a dietician and I knew more about the diet than they did. They were no help at all.” That is really a terribly frustrating thing for patients. So, clinicians want to make sure that they send their patients to somebody who has a fair degree of knowledge, interest, and expertise in celiac disease. Unfortunately, this expertise is just not that common these days.

DR. MUSHLIN: Ms. Dennis, how many hours do you normally have to spend to get a newly diagnosed patient with true celiac disease, not just gluten sensitivity, up to speed assuming they have normal intelligence, at least a high school education, and some kind of familiarity with the basics of nutrition. How many hours might it take for you to meet with them? Often when physicians send a patient for a consultation, it’s helpful to tell the patient that they may need to be seen a few times to get it right because sometimes patients are surprised or dismayed that 20minutes with someone hasn’t fixed them.

MS. DENNIS: In this hospital setting, I’m not able to see patients as often or for as long of a period of time as I would like, and that’s common across many, many nutrition practices. We have an hour to educate patients initially. In an ideal world, the patients would be back within a few weeks for part 2 for at least an hour, and then they would check in periodically for the next 3months, 6months, and then yearly for a wellness check.

You can absolutely not do this in one session, and so, I’ve designed nutrition counseling sessions to give patients a tremendous amount of information that they can read. I also instruct them to explore reputable sites, read the material that we’ve created, and then come back with questions. I always link them to a local support group, which is absolutely critical for the management of this lifestyle adjustment. They can’t cope with the condition alone, and they certainly can’t do it on a few hours of nutrition consulting.

DR. MUSHLIN: Are you folks doing group counseling yet at your institution? For example, patients who’ve spent an hour or greater with you can come back in a group setting to get their questions answered, have an open discussion, and obtain support from other fellow patients or from other individuals following the same diet.

MS. DENNIS: Our clinic visits are one-on-one, but we do offer patient education nights 3 times a year where 10 to 40 people join us, and one of the doctors and I sit and answer questions for an hour and a half. That is a great experience for the patients. It’s always a very warm environment, and we again connect them to our larger support group that serves all of New England, the Healthy Villi, and they’re able to attend conferences, expos, or large meetings at least 3 times a year.

DR. MUSHLIN: I certainly think that if the paradigms of helping patients with chronic ongoing illness can be managed, their illnesses are going to gravitate more and more toward exactly those kinds of group support models.

MS. DENNIS: I agree.

DR. MUSHLIN: Dr. Leffler, you’ve mentioned briefly that in follow-up with your patients who have celiac disease, you need to be careful or be aware of the possibility of low bone density, and you also mentioned that they need vaccinations. What vaccinations do they require and why?

DR. LEFFLER: One of the things that is not widely known about celiac disease is that it’s actually associated with functional hyposplenism. So, people with celiac disease have an increased risk of infections—primarily those involving encapsulated organisms but also other infections—and these infections can be more severe. Our general recommendations are to vaccinate all celiac patients for flu and pneumococcus regardless of their age. Unfortunately, we have seen cases of very severe pneumococcal sepsis in otherwise totally healthy immunocompetent patients with celiac disease. So, it is something that we recommend routinely to all of our patients.

DR. MUSHLIN: Regarding the unusual association of celiac disease with other medical situations, one of my colleagues here saw a patient with pulmonary hemosiderosis who happened to have celiac disease. Are there other unusual conditions that are associated with celiac disease?

DR. LEFFLER: Yes. That pulmonary condition is called Lane-Hamilton syndrome. It is quite rare, but we’ve seen a few cases of it.

One of the fascinating things about celiac disease is that it can affect any organ system in the body. You can see effects in the central nervous system, skin, bones, kidneys, reproductive system, lungs, and heart, and there are a number of reasons why celiac disease can be so far-reaching.

Part of it is just that chronic nutritional deficiencies can lead to widespread problems, but more fundamentally, people with celiac disease produce antibodies to tTG. That’s the blood test that is most commonly ordered—the IgA anti-tTG blood test. The enzyme tTG is found in all parts of the body. Its main job is to crosslink collagen. It’s very active in wound repair and building connective tissue, and when antibodies attack this enzyme, inflammation can occur anywhere in the body. Presumably, depending on the exact type of antibodies produced and polymorphisms in tTGs, you can have a direct autoimmune effect that’s triggered in the intestine but attacks the brain or virtually any other organ.

Gluten ataxia is a cardinal well-known phenomenon where you have cerebellar inflammation and cerebellar atrophy due to the celiac reaction. You can have dermatitis herpetiformis, which is an inflammatory reaction of the skin that mostly affects extensor surfaces. So, you have this autoimmune reaction that can attack any part of the body but starts in the intestine. Once you get celiac disease under control, for example by going on a gluten-free diet, these antibody levels decrease and the autoimmune reactions cease just as they do in the intestine. This is really a very unique way of thinking about an autoimmune disease.

DR. MUSHLIN: Because we’re talking so much about antibodies, do you follow antibody titers in people you’ve placed on a gluten-free diet?

DR. LEFFLER: Yes, I do. I follow them not because they’re really wonderful at monitoring celiac disease, because they’re not. There is plenty of research including some that we’ve done ourselves^4,5 that shows that they’re not great at telling, for instance, recent gluten exposure or the degree of intestinal healing. There are lots of people who have completely normal antibody levels, but their intestine’s ability to heal is significantly damaged and vice versa. Some people still have mild elevations in their antibody levels, but their intestine looks pretty good.

On the other hand, there’s really no other tool that we have, and if you have somebody with antibody levels that are persistently elevated and never drop, or drop slightly but are still 2 to 3 times the upper limit of normal, you can be fairly certain that gluten is sneaking in somewhere, and they may not know it. They may be doing their best to follow a gluten-free diet. It could be something as simple as a single generic medication or a supplement that has gluten in it that they’re taking on a daily basis. We’ve seen issues of that sort, but if their antibody level is still high, it’s very helpful as a red flag that something’s not going right.

The first thing I’ll do is send them back to see Ms. Dennis to review the diet and see where the problems are cropping up. That will fix many of the problems, but it can take an awful lot of detective work to sort through basically everything that they’re putting in their mouth and see where that bit of gluten might be.

DR. MUSHLIN: So let’s say the family practitioner diagnoses celiac disease based on the patient’s history and physical findings, and the tTG antibody test is highly positive. The practitioner then sends the patient to a nutritionist, and the patient goes on a gluten-free diet. How should that family practitioner then follow up with the patient? You mentioned immunizations—influenza yearly and Pneumovax. What else should be routinely done by that practitioner, for example, in a rural community where the patient might not have access to a specialist?

DR. LEFFLER: I want to just mention that even with a positive antibody level, endoscopy is still necessary at the beginning for diagnosis. The standard of care for celiac disease these days includes checking celiac serologies approximately every 3 to 6months until they normalize, which depends on how high they are at the beginning. Some people start off with a relative titer of 1000, and some start off with a relative titer of 50. Obviously, the latter will normalize much more quickly.

What you want to see is an improvement in those levels, so you follow them approximately every 6months until they normalize. Then you perform a celiac blood test approximately every year just to make sure that the levels are staying low and that something hasn’t changed such that the patient suddenly has an elevated level. At least 1 bone mineral density test should be performed approximately 1 year after diagnosis once their vitamin D and any other nutritional deficiencies have been repleted. We can mention the nutrients to check in a second, and if those are normal, then the patient can go back to the bone mineral density recommendations for the regular population.

If their bone mineral density is low, then you want to keep a closer eye on them depending on how low it is. You can see a lot of improvement in bone mineral density in the first year after diagnosis with celiac disease, which is why we don’t typically check bone density right off the bat unless the patient has had fractures or something that we’re really worried about. It’s only the residual osteopenia or osteoporosis that they have after a year that we would treat differently.

Even after the initial dietary counseling, we strongly recommend that patients check in with their dietician once a year. Again, a gluten-free diet is a really big change. It’s tough. Things change all the time, and by following up with a specialist, you can tell them about how the foods you eat have changed. New recommendations on a yearly basis are also recommended.

As for vitamins, the most common nutrient deficiencies in people with celiac disease are currently vitamin D, iron, and zinc. Zinc is not one that’s commonly on people’s radar, but it is actually responsible for a lot of the hair and skin manifestations that people with celiac disease complain about and potentially responsible for some of the immune dysregulation as well.

Regarding consumer access, it is important to find safe gluten-free foods that are not cross-contaminated. We now have a Food Allergen Labeling and Consumer Protection Act in place that states that if wheat protein is in an FDA-regulated food, it must be labeled as such on the package. That applies to FDA foods but not USDA foods. Dieticians know the difference between these two and can educate their patients, but it’s not obvious by just reading a label.

The most obvious sources of gluten are wheat, rye, barley, malt, oats (unless they are specifically labeled and processed such that they are gluten free), and brewer’s yeast. These are easily identifiable, but it takes a little bit of education to get familiar with hidden gluten sources. One of the primary things that a person can do is make sure that their grains and flour-based products are labeled “gluten free” to help avoid some of the risks of cross-contamination that come when gluten-free grains are contaminated with wheat, rye, or barley during the farming, processing, or milling practices that typically occur in this country.

DR. MUSHLIN: So let’s say I’ve got a patient who says to me, “Doc, I’ve got celiac disease. Can I ever eat out again? Can I ever go to a restaurant?” How would you advise them?

MS. DENNIS: I have celiac disease myself, and yes you can absolutely eat out. I was diagnosed 22 years ago. So much has changed in these last 2 decades that makes life a lot easier for us, but you do have to pay attention when dining out, not only to the ingredients that are going into the food but also to the preparation technique used.

If a newly diagnosed person goes out to eat, they would want to first choose a celiac-friendly restaurant, meaning a restaurant that has a gluten-free menu. Even then, I would suggest asking questions related to the ingredients and the preparation methods. For example, it’s pretty common knowledge among people with celiac disease that fryers are contaminated, but what’s less commonly known is that scrambled eggs can often be mixed with pancake batter to make them fluffy and increase their volume. Roasts and beef cuts that are served in a restaurant are often held in a broth that contains wheat, prior to being served. Baked potatoes may be put into a fryer just before serving them at the table.

It’s important that in the kitchen, where the food is being prepared, different utensils and skillets are used, and that the person preparing the food is paying attention to what cutting boards he/she is using and not cross-contaminating with other gluten-containing products. All of this being said, there is much more opportunity for people to dine out these days. However, you have to be very, very careful, and there are resources that can lead you to restaurants that are more inclined to understand food allergies and make allowances and substitutions for those on the gluten-free diet.

DR. MUSHLIN: Ms. Dennis, would you elaborate on how to access those resources, and can you also discuss a few reputable websites that can be used by people with gluten sensitivity?

MS. DENNIS: There are a number of national organizations that are deeply committed to celiac disease, the gluten-free diet, and those with non-celiac gluten sensitivity. In no particular order, these include the Celiac Disease Foundation (www.celiac.org), the Gluten Intolerance Group (www.gluten.net), the Celiac Sprue Association of the United States (CSA/USA, Inc; www.csaceliacs.info), the American Celiac Disease Alliance (americanceliac.org), and the National Foundation for Celiac Awareness (www.celiaccentral.org). These can all be easily found by a Google search. Each of them contains multiple listings of resources including restaurants, information about dining out, tips on how to eat when traveling, nutrition information, hidden gluten sources, blogs, and how to budget on the gluten-free diet. Many of them list celiac centers across the United States and describe how to find specific clinicians who are experts in this field. All of these are reputable sites.

I should mention that we have also launched a multi-level website especially designed for the nutritional management of celiac disease: CeliacNow.org. It’s useful for anyone on the gluten-free diet as well as practitioners who want to gain more information.

Back to your original question about dining out in particular, there are 2 resources that I recommend to patients. One of them is TriumphDining.com. Not only do they list grocery stores and food sources across the state, they also list restaurants. CeceliasMarketplace.com is also another excellent website. Both of these sites also offer books on the topic. Finally, the forum at www.celiac.com is a place that most people find almost immediately when they’re diagnosed.

DR. MUSHLIN: Good. Is there any special designation for people who do nutritional work such as yourself who specialize in celiac counseling, or can any registered nutritionist counsel someone appropriately?

MS. DENNIS: They are actually working on a certification program for the counseling of patients with celiac disease. I joined a taskforce about 5 years ago that developed nutritional guidelines for the Academy of Nutrition and Dietetics.³ These guidelines are available if dieticians want to train themselves on how to counsel a patient on the gluten-free diet, beginning with the initial visit through the follow-up visits. The guidelines include laboratory tests, case studies, and multiple patient handouts, and they constitute the industry’s major educational piece on celiac disease. Beyond that, you can examine books, articles, etc, written by a number of experts in the field. There’s currently no certification.

DR. LEFFLER: A lot of patients will come to me saying, “I saw a dietician and I knew more about the diet than they did. They were no help at all.” That is really a terribly frustrating thing for patients. So, clinicians want to make sure that they send their patients to somebody who has a fair degree of knowledge, interest, and expertise in celiac disease. Unfortunately, this expertise is just not that common these days.

DR. MUSHLIN: Ms. Dennis, how many hours do you normally have to spend to get a newly diagnosed patient with true celiac disease, not just gluten sensitivity, up to speed assuming they have normal intelligence, at least a high school education, and some kind of familiarity with the basics of nutrition. How many hours might it take for you to meet with them? Often when physicians send a patient for a consultation, it’s helpful to tell the patient that they may need to be seen a few times to get it right because sometimes patients are surprised or dismayed that 20minutes with someone hasn’t fixed them.

MS. DENNIS: In this hospital setting, I’m not able to see patients as often or for as long of a period of time as I would like, and that’s common across many, many nutrition practices. We have an hour to educate patients initially. In an ideal world, the patients would be back within a few weeks for part 2 for at least an hour, and then they would check in periodically for the next 3months, 6months, and then yearly for a wellness check.

You can absolutely not do this in one session, and so, I’ve designed nutrition counseling sessions to give patients a tremendous amount of information that they can read. I also instruct them to explore reputable sites, read the material that we’ve created, and then come back with questions. I always link them to a local support group, which is absolutely critical for the management of this lifestyle adjustment. They can’t cope with the condition alone, and they certainly can’t do it on a few hours of nutrition consulting.

DR. MUSHLIN: Are you folks doing group counseling yet at your institution? For example, patients who’ve spent an hour or greater with you can come back in a group setting to get their questions answered, have an open discussion, and obtain support from other fellow patients or from other individuals following the same diet.

MS. DENNIS: Our clinic visits are one-on-one, but we do offer patient education nights 3 times a year where 10 to 40 people join us, and one of the doctors and I sit and answer questions for an hour and a half. That is a great experience for the patients. It’s always a very warm environment, and we again connect them to our larger support group that serves all of New England, the Healthy Villi, and they’re able to attend conferences, expos, or large meetings at least 3 times a year.

DR. MUSHLIN: I certainly think that if the paradigms of helping patients with chronic ongoing illness can be managed, their illnesses are going to gravitate more and more toward exactly those kinds of group support models.

MS. DENNIS: I agree.

DR. MUSHLIN: Dr. Leffler, you’ve mentioned briefly that in follow-up with your patients who have celiac disease, you need to be careful or be aware of the possibility of low bone density, and you also mentioned that they need vaccinations. What vaccinations do they require and why?

DR. LEFFLER: One of the things that is not widely known about celiac disease is that it’s actually associated with functional hyposplenism. So, people with celiac disease have an increased risk of infections—primarily those involving encapsulated organisms but also other infections—and these infections can be more severe. Our general recommendations are to vaccinate all celiac patients for flu and pneumococcus regardless of their age. Unfortunately, we have seen cases of very severe pneumococcal sepsis in otherwise totally healthy immunocompetent patients with celiac disease. So, it is something that we recommend routinely to all of our patients.

DR. MUSHLIN: Regarding the unusual association of celiac disease with other medical situations, one of my colleagues here saw a patient with pulmonary hemosiderosis who happened to have celiac disease. Are there other unusual conditions that are associated with celiac disease?

DR. LEFFLER: Yes. That pulmonary condition is called Lane-Hamilton syndrome. It is quite rare, but we’ve seen a few cases of it.

One of the fascinating things about celiac disease is that it can affect any organ system in the body. You can see effects in the central nervous system, skin, bones, kidneys, reproductive system, lungs, and heart, and there are a number of reasons why celiac disease can be so far-reaching.

Part of it is just that chronic nutritional deficiencies can lead to widespread problems, but more fundamentally, people with celiac disease produce antibodies to tTG. That’s the blood test that is most commonly ordered—the IgA anti-tTG blood test. The enzyme tTG is found in all parts of the body. Its main job is to crosslink collagen. It’s very active in wound repair and building connective tissue, and when antibodies attack this enzyme, inflammation can occur anywhere in the body. Presumably, depending on the exact type of antibodies produced and polymorphisms in tTGs, you can have a direct autoimmune effect that’s triggered in the intestine but attacks the brain or virtually any other organ.

Gluten ataxia is a cardinal well-known phenomenon where you have cerebellar inflammation and cerebellar atrophy due to the celiac reaction. You can have dermatitis herpetiformis, which is an inflammatory reaction of the skin that mostly affects extensor surfaces. So, you have this autoimmune reaction that can attack any part of the body but starts in the intestine. Once you get celiac disease under control, for example by going on a gluten-free diet, these antibody levels decrease and the autoimmune reactions cease just as they do in the intestine. This is really a very unique way of thinking about an autoimmune disease.

DR. MUSHLIN: Because we’re talking so much about antibodies, do you follow antibody titers in people you’ve placed on a gluten-free diet?

DR. LEFFLER: Yes, I do. I follow them not because they’re really wonderful at monitoring celiac disease, because they’re not. There is plenty of research including some that we’ve done ourselves^4,5 that shows that they’re not great at telling, for instance, recent gluten exposure or the degree of intestinal healing. There are lots of people who have completely normal antibody levels, but their intestine’s ability to heal is significantly damaged and vice versa. Some people still have mild elevations in their antibody levels, but their intestine looks pretty good.

On the other hand, there’s really no other tool that we have, and if you have somebody with antibody levels that are persistently elevated and never drop, or drop slightly but are still 2 to 3 times the upper limit of normal, you can be fairly certain that gluten is sneaking in somewhere, and they may not know it. They may be doing their best to follow a gluten-free diet. It could be something as simple as a single generic medication or a supplement that has gluten in it that they’re taking on a daily basis. We’ve seen issues of that sort, but if their antibody level is still high, it’s very helpful as a red flag that something’s not going right.

The first thing I’ll do is send them back to see Ms. Dennis to review the diet and see where the problems are cropping up. That will fix many of the problems, but it can take an awful lot of detective work to sort through basically everything that they’re putting in their mouth and see where that bit of gluten might be.

DR. MUSHLIN: So let’s say the family practitioner diagnoses celiac disease based on the patient’s history and physical findings, and the tTG antibody test is highly positive. The practitioner then sends the patient to a nutritionist, and the patient goes on a gluten-free diet. How should that family practitioner then follow up with the patient? You mentioned immunizations—influenza yearly and Pneumovax. What else should be routinely done by that practitioner, for example, in a rural community where the patient might not have access to a specialist?

DR. LEFFLER: I want to just mention that even with a positive antibody level, endoscopy is still necessary at the beginning for diagnosis. The standard of care for celiac disease these days includes checking celiac serologies approximately every 3 to 6months until they normalize, which depends on how high they are at the beginning. Some people start off with a relative titer of 1000, and some start off with a relative titer of 50. Obviously, the latter will normalize much more quickly.

What you want to see is an improvement in those levels, so you follow them approximately every 6months until they normalize. Then you perform a celiac blood test approximately every year just to make sure that the levels are staying low and that something hasn’t changed such that the patient suddenly has an elevated level. At least 1 bone mineral density test should be performed approximately 1 year after diagnosis once their vitamin D and any other nutritional deficiencies have been repleted. We can mention the nutrients to check in a second, and if those are normal, then the patient can go back to the bone mineral density recommendations for the regular population.

If their bone mineral density is low, then you want to keep a closer eye on them depending on how low it is. You can see a lot of improvement in bone mineral density in the first year after diagnosis with celiac disease, which is why we don’t typically check bone density right off the bat unless the patient has had fractures or something that we’re really worried about. It’s only the residual osteopenia or osteoporosis that they have after a year that we would treat differently.

Even after the initial dietary counseling, we strongly recommend that patients check in with their dietician once a year. Again, a gluten-free diet is a really big change. It’s tough. Things change all the time, and by following up with a specialist, you can tell them about how the foods you eat have changed. New recommendations on a yearly basis are also recommended.

As for vitamins, the most common nutrient deficiencies in people with celiac disease are currently vitamin D, iron, and zinc. Zinc is not one that’s commonly on people’s radar, but it is actually responsible for a lot of the hair and skin manifestations that people with celiac disease complain about and potentially responsible for some of the immune dysregulation as well.