Ask the Celiac Doctor

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Celiac expert Peter Green, MD, talks with GF&M editor-in-chief Alicia Woodward about celiac disease, quality of life issues and the idea of personalized treatment.

Gastroenterologist Peter H.R. Green, MD, is one of the nation’s leading experts and researchers on celiac disease. He is director of the Celiac Disease Center at Columbia University Medical Center in New York City, where he serves as the Phyllis & Ivan Seidenberg Professor of Medicine. He is also the co-author of Gluten Exposed (Harper Collins).

GF&M: The Celiac Disease Center has conducted research that indicates the gluten-free diet can negatively impact people’s quality of life. Tell us about that.

Dr. Green: Some people with celiac disease adhere to a gluten-free diet with an approach that reduces their quality of life. One study we conducted revealed that people with the greatest knowledge and the most vigilance about sticking to the diet had the worst quality of life. You know, it’s great that more people are diagnosed but it’s not productive that the diet is making them crazy.

When you say crazy, are you talking about anxiety, depression, that sort of thing?

Yes, I’m talking about anxiety, depression and being stressed out. I’m talking about people who develop maladaptive eating behaviors, like they don’t go out and eat, they don’t participate in social activities, they’re only comfortable when they intensely drill the waiter and the chef. These maladaptive eating behaviors could be forerunners of eating disorders. We’re trying to determine how common this is and trying to figure out ways to improve people’s quality of life.

But people with celiac disease are supposed to be really careful about gluten.

I’m not talking about relaxing a strict gluten-free diet. I’m talking about hyper-vigilance. I’m talking about obsessive behavior—like not ever eating out, taking your food everywhere, not trusting anyone, special pots and pans in the household kitchen. You know, that’s hyper-vigilance and is unhealthy.

Even a little bit of gluten can cause mucosal damage. How do you reconcile that with telling people they shouldn’t be hyper-vigilant?

People with celiac disease need to avoid gluten. They need to be on a strict gluten-free diet, yes, but they also need to be able to enjoy their lives. Intermittent ingestion of small amounts of gluten is inevitable. For some, hyper-vigilance comes at a great price and it’s misdirected. And it’s not clear that people who are hyper-vigilant are better off than people who aren’t as vigilant.

What do you mean?

Most people with celiac disease really don’t know how they’re getting on; they don’t know if they have healed their intestinal lesion. We know that some people who get a little bit of gluten can get as sick as a dog—but they can have a normal biopsy. There needs to be a personalized approach to each individual, in which the person works with their senior doctor and their dietitian to heal the mucosa, to eliminate symptoms and to have a happy life.

Most people judge their success in adhering to the gluten-free diet on whether or not they get sick, or “glutened.” Should we be judging our success on the gluten-free diet by the health of our gut mucosa?

Yes. There’s a difference between an immediate reaction to gluten and the long-term risk. We’ve shown that people with celiac disease whose mucosa has not healed are at an increased risk of developing lymphoma. In our research, persistent villous atrophy leads to increased rates of lymphoma and fracture risk. We are also aware that some people, even those who have normalized their mucosa, can get very sick with a small amount of contaminating gluten. Although they may have totally healed their mucosa, their villi, they will get very sick if they get a small (or a larger) amount of gluten.

Again, eating a little gluten and getting sick may not impact a normal biopsy.

Some people seem to become even more sensitive to gluten after they go on the gluten-free diet.

They do. We now understand the mechanism. It’s due to cytokine release, which causes the intense symptoms that some people experience, like headache, fatigue, nausea and vomiting. You’re diagnosed with celiac disease, go on a gluten-free diet, unintentionally get a little bit of gluten, the cytokines pour out and you get sick. This was shown in the research related to the celiac vaccine that’s under development.

But people should realize that if they get symptoms, it might not be because they ate gluten. People with celiac disease can get sick for other reasons apart from gluten. For example, people with celiac disease are more likely to be fructose intolerant. So you’re eating a honey-sweetened gluten-free cereal and you get sick. Was it gluten or the honey (which contains fructose)? Determining what is making you sick is another opportunity for a personalized approach.

A personalized approach—are you talking about a type of personalized medicine?

Technically speaking, personalized medicine is the concept of directing therapy based on a patient’s particular genes. We’re not there yet with celiac disease. But we do know that some people are more sensitive to gluten than others. We also know that each individual has symptoms that are individual to that person. We should be able to work out what the individual symptoms are related to and how much they’re related to gluten or something else like fructose.

People need to get a follow-up biopsy to see if their way of life has normalized their mucosa. I advocate people getting a follow-up biopsy because it confirms that whatever they’re doing with the diet is fine. If their mucosa hasn’t normalized, they should go to a dietitian and work out what to do. If a follow-up biopsy is normal, the individual is reassured that their adherence to the diet is compatible with the full treatment of their celiac disease. That’s a good example of personalized medicine.

How does the blood test fit into this?

The blood test does not reflect mucosal healing. Yes, if the blood test is zero, there’s a high correlation with healing. But we know that normalization of the blood test results does not predict healing of the mucosa. If you have celiac disease and your blood test is normal, that means you’re on a gluten-free diet.

The biopsy is still considered the gold standard to confirm a celiac diagnosis. When would you normally recommend a follow-up biopsy?

It depends on the results of the follow-up blood test. The antibodies have to normalize. If they’re not normal, the patient is still getting gluten. The antibody level should be normal within a year of going gluten-free. They’re often normal before that.

I suggest a follow-up biopsy when patients are at their best, which is typically about two years after diagnosis if all goes well. The patient is eating a gluten-free diet, their antibody level is normal and they’re doing very well. If the biopsy results come back normal, it’s reassuring. If not, the patient should re-consult with an experienced dietitian to determine where they’re going wrong. Some individuals are very sensitive to little bits of gluten and a dietitian can help them figure out where and when they’re getting exposed.

The Celiac Disease Center conducted research on providers doing endoscopies and analyzing biopsies. You were a part of that study. Doesn’t lack of standardization in this area present an additional challenge?

Yes. So we were very interested in this. There are multiple studies showing there are still delays in getting a celiac diagnosis and it can be due to doctors.

As an example, patients will come to the Celiac Disease Center after having undergone an endoscopy and they’re still not sure they have celiac disease. We look at their biopsy results and find that maybe just one piece was taken during the procedure. So there weren’t enough pieces to obtain any viable information. Four to six biopsies are recommended, as well as biopsies from the first part or bulb of the duodenum. We used to teach that biopsies should not be taken from the bulb. Our study showed that it is absolutely necessary.

In addition, the standard of quality varies. We saw doctors turning over the endoscopy room quickly, taking shortcuts and not taking the full number of pieces. If you’re the last patient of the day, the doctor may be fatigued. And then there’s the pathology—we reviewed a hundred biopsies. When the biopsies were originally interpreted at a university medical center, we had a high degree of agreement. When the biopsies were performed at a freestanding endoscopy unit or a community endoscopy facility, our agreement with the findings of the pathology report was not as good.

Given this problem, what would you advise patients about the endoscopy?

My advice would be that people go to celiac centers or to university medical centers to get their endoscopies. I understand that not everyone has the benefit of living near a celiac center or is able to get this level of care but, if at all possible, people with celiac disease should try to do this.

What are the guidelines for endoscopy for celiac disease?

The endoscopy is a way to assess damage or inflammation to the small intestines by taking multiple specimens that are biopsied. The guidelines of the American Gastroenterological Association, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the American College of Gastroenterology recommend taking four to six pieces from the duodenum and two from the bulb for biopsy. The guidelines also recommend taking one “bite” per pass of the forceps in some parts of the intestine. Typically, doctors take two “bites” per pass of the forceps.

Generally speaking, are doctors who perform endoscopies adhering to these guidelines?

Our research shows there’s a wide range of performance of a duodenal biopsy among providers. There are multiple reasons why endoscopies aren’t performed according to the guidelines. This is one of the directions of our research. We think the more research, the more studies that are published, the more we get out there and talk to the medical community and patients, the more informed everyone is, including the doctors who are performing biopsies and diagnosing celiac patients. The United States is now the foremost in the world in producing research on celiac disease. Ultimately, this is good news for everyone in this country who has celiac disease.

Should celiac patients be undergoing an endoscopy on a more regular schedule? Should they work with their gastroenterologist to get on a schedule?

It depends on the patient. I see new patients who say, my doctor does a biopsy every year. When I ask them, what’s the outcome of that, they say they still have celiac disease. Well, that’s not helping anyone. Are the biopsy results normal or not? In this case, it sounds like they are abnormal. So when they’re abnormal, there’s got to be some action in response to that, like work with the dietitian. If the antibodies in the blood are abnormal, there’s got to be some kind of action. If the vitamin levels are low, there’s got to be some action. This is a personalized approach.

And that’s the other thing—too few patients have a registered dietitian helping them with the diet. There are two important things to know when you’re on a gluten-free diet. One is knowing what to eat. The other is knowing what to avoid. Some people may think they know everything but if their blood or biopsy results show otherwise, an experienced dietitian can help.

Celiac disease remains underdiagnosed but there’s been a lot of progress in increasing the diagnostic rate.

Yes. It’s now thought that more than half the people with celiac disease in this country are diagnosed. We’ve been really obsessed with trying to increase the rate of diagnosis and that’s great. But now we owe it to people to help them live gluten-free without decreasing their quality of life. What’s the point of diagnosing someone when it means they go on to have 40 years of misery because they’re so stressed out about the diet? This is a difficult topic—but I think we’ve got to look at this stuff. It’s why we’re working so hard to help develop a medication that’s appropriate for people with celiac disease. We’d like to ease the burden of the gluten-free diet. We’ve got to help people learn how to handle this very important disease.

Alicia Woodward is editor-in-chief of Gluten Free & More magazine.