Celiac Disease in Children: Experts Clarify Diagnosis and Management Recommendations

William F. Balistreri, MD; Ivor D. Hill, MD, MB ChB; Alessio Fasano, MD


October 25, 2016

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When Celiac Disease Is Suspected in Children

William F. Balistreri, MD: Hello. I am Dr Bill Balistreri, professor of pediatrics at the University of Cincinnati in the Cincinnati Children's Hospital. We are here today on Medscape via Skype to discuss the recently published recommendations[1] for the diagnosis and management of gluten-related disorders in children and adolescents.

Let me introduce my colleagues. Dr Alessio Fasano is the W. Allan Walker Chair of Pediatric Gastroenterology and Nutrition in the Department of Pediatric Gastroenterology and Nutrition of Massachusetts General Hospital, Harvard Medical School. Dr Ivor Hill is professor of clinical pediatrics in the Department of Gastroenterology at The Ohio State University College of Medicine.

Dr Hill recently assembled a group of experts on celiac disease to offer guidance to clinicians in their efforts to distinguish celiac disease from nonceliac gluten sensitivity and other disorders, such as irritable bowel syndrome. Ivor, could you summarize your approach and underscore why it is so important to accurately differentiate these disorders?

Ivor D. Hill, MD, MB ChB: In essence, we want to distinguish between celiac disease, a wheat allergy, and nonceliac gluten sensitivity. The importance of distinguishing between these three conditions is this, for a start: If you have celiac disease, it carries certain implications for long-term adverse health outcomes, and specific kinds of follow-up are needed for that condition. If you have a wheat allergy, it means you have to follow a less restrictive diet, and there is a good chance that you could actually recover from a wheat allergy. This nonentity of "nonceliac gluten sensitivity" has become a very hot topic. We are not sure exactly how many people have this condition, and we think it may be a collection of responses that people have when they remove gluten from their diets. It is important to distinguish between the three conditions because it dictates how you are going to manage those patients and their long-term potential outcomes.

Dr Balistreri: For clinicians who have patients with gastrointestinal or systemic manifestations, how do they approach these children?

Dr Hill: It's very important to understand that there is significant overlap in the presentation of the symptoms of all three conditions. It is very important to try to identify specifically which condition a child has. We strongly recommend that if you have a patient whom you suspect has one of these conditions, you test before you treat.

We strongly recommend that if you have a patient whom you suspect has one of these conditions, you test before you treat.

The test for celiac disease is pretty specific. We recommend using a tissue transglutaminase (TTG) together with a serum IgA level. If that is elevated, do a biopsy to confirm celiac disease. Wheat allergy is more difficult to confirm. There are skin-prick tests that can be done for wheat allergy, but they are not very sensitive or specific, and this often means that you have to do a food challenge to diagnose wheat allergy. Nonceliac gluten sensitivity is a diagnosis of exclusion. You have to exclude celiac disease and you have to make sure that the patient does not have a wheat allergy before you can consider the diagnosis of nonceliac gluten sensitivity.

Dr Balistreri: You made a point that all of this workup leads to an intestinal biopsy. Our colleagues in Europe have discussed the potential approach of making the diagnosis without a biopsy. Can you give us a little bit of insight on that?

Dr Hill: In the United States, we are still a little concerned about not doing a biopsy.

The recommendation from Europe is that if the TTG level is more than 10 times the upper limit of normal, and a second test shows a positive endomysial antibody, together with the current HLA-DQ2, DQA haplotypes in a symptomatic patient, you could confidently make a diagnosis of celiac disease.

In the United States, we are concerned that there is no standardization of the tests for the celiac serology. There is quite a bit of variability among the various companies that offer this test. We still feel more comfortable using a biopsy to confirm the diagnosis. It is important to confirm the diagnosis, because you are subjecting that individual to a strict gluten-free diet for life, which carries a lot of implications in and of itself.

New Pediatric Recommendations

Dr Balistreri: That leads me to Dr Fasano. Concerns have been raised about the lack of effective long-term management programs to optimize the treatment of patients with celiac disease. For example, recent reports indicate that optimal follow-up and care of patients are not driven by evidence but are largely based on perceived benefits. We all have these ideas in our minds. Last month, Dr Fasano and colleagues published a report on evidence-informed expert recommendations[1] for the management of celiac disease in children in which they address these questions about which tests and practices should become standard of care for management and monitoring of celiac disease. Alessio, could you review these recommendations for us?

Alessio Fasano, MD: First of all, this was the work of the late John Snyder who unfortunately left us prematurely. He was the one who assembled this group of individuals based on the clinical sense that recommendations for managing celiac disease were not clear. There were discrepancies and we didn't have a unified way to approach the management of celiac disease in children. We eventually decided to sit down and form six specific categories: bone health, hematologic issues, endocrine problems, liver disease, nutrition, and testing. We went through the literature; we reviewed 600 publications, of which only 72 studies were deemed to be appropriately designed to be included in these evidence-based expert recommendations.

An expert panel was assembled to develop the recommendations. Of course, all of the conditions were newer and did not have guidelines, and there could be discrepancies among the experts, but surprisingly, out of 25 questions, 24 were unanimously answered in a blind fashion by the experts. There was a pretty strong unanimous response in the way that we perceived the evidence and made appropriate recommendations.

In terms of bone health, there was not an issue. For example, for routine screening for bone health, we considered discussing that the grade of evidence was moderate and the strength of recommendations that we made was low. On the other hand, counseling about age-appropriate intake of calcium and vitamin D was very highly regarded and there was a strong recommendation there.

For the hematologic domain, screening for anemia was the highest recommendation with strong evidence. For folate deficiency, however, the evidence was low and our recommendation on the matter was weak. Initially, even the National Institutes of Health (NIH) Consensus Conference[2] created a discrepancy about the recommendation to not screen for celiac disease in people with type 1 diabetes, whereas we concluded that the evidence was extremely strong.

In terms of liver disease, the evidence for routine screening for AST [aspartate aminotransferase] and ALT [alanine aminotransferase] was strong and our recommendation was moderate. For hepatitis B virus, immunization status was another major issue that we dealt with. There was definitely a recommendation in that domain.

Most of the time we spent and most of the real controversy was on testing for celiac disease. Although the TTG is a robust diagnostic test and is validated and accepted by the US Food and Drug Administration, we concluded that in terms of monitoring, unfortunately it does not have the kind of strength that we perceived it to have at the beginning. The studies published in the literature since that time have suggested that this is the case.

Dr Balistreri: I was surprised that many of the practices that we have established in our own world were not supported by the evidence. I think this document will provide some very useful guidelines that hopefully will allow us to follow these patients in a very cost-effective manner.

I was surprised that many of the practices that we have established in our own world were not supported by the evidence.

Ivor, you and your colleague wrote an editorial[3] in response to the guidelines. Could you give us your perspective on these recommendations? 

Dr Hill: To me, the strength of this publication was that it is more likely to standardize care. If you look at the care of patients with celiac disease, both at the time of diagnosis and subsequently with follow-up, even among our own division, which is a very large division at Nationwide Children's Hospital, there is extreme fragmentation of care. It is not uniform at all. This publication gives us a basis on which to standardize care, which I think will lead to improved outcomes for our patients with celiac disease. It has been very useful for knowing what to do at the time of diagnosis: which tests we should do, how often we should follow these patients, and which tests should be done at follow-up, at the 6-month and annual visits. I think it will improve the long-term outcomes of these patients. It is a very important publication from my point of view. 

Dr Balistreri: One of the questionable areas, as Dr Fasano mentioned, was bone health. We have routinely measured bone density and all of the associated minerals and vitamins. Your recommendations have allowed us to cut back and, I believe, to be cost-effective.

Alessio, what was the most problematic area for your group? Which topic has the least evidence yet probably is given the most attention in clinical practice?

Dr Fasano: It definitely was the testing. Before, we always used the TTG, for both diagnosis and management of celiac disease, with the perception that it was as robust in both domains as we anticipated. Both the review and the evidence that is now coming out suggest that the TTG antibody is undisputedly one of the most formidable tests that we have in our toolbox for the diagnosis of celiac disease, in terms of sensitivity and specificity. Very few tests are as good as the TTG; however, when doctors use it for follow-up, the discrepancy between what we see in terms of the test and the actual repair of the celiac arthropathy becomes wide—so much so that now we have to review how we manage kids with celiac disease. Our concern now, which we just published recently, [Editor's note: This study is still in press.] is that up to 20% of these kids will not repair after a good year of compliance with a gluten-free diet, despite the TTG being negative. We do not know what kind of consequences these kids might have, particularly in terms of growth, in such a crucial time of their lives.

The Future: Are We Gluten Free?

Dr Balistreri: What is on the horizon? In real life, we have patients who are extraordinarily sensitive to gluten who are inadvertently exposed at various times. Is there a way to monitor the dietary intake, to have a gluten-sensing dog, or fecal antigen tests or some way that we can prevent these children from getting into difficulty? That would be our final comment from both of you.

Dr Hill: Alessio makes a very strong point about the fact that we just do not know how many of our children are repairing completely from the villous atrophy. This has opened up a whole new can of worms and is something that we need to start looking at in the future. Are we following these children correctly? Are we monitoring them? There is no doubt about it that the long-term adverse health implications associated with celiac disease are not related to symptoms or to persistently elevated TTG levels, but they are strongly related to persistent villous atrophy. That is number one.

There is no doubt about it that the long-term adverse health implications associated with celiac disease are not related to symptoms or to persistently elevated TTG levels, but they are strongly related to persistent villous atrophy.

A very interesting paper has just come out in the American Journal of Gastroenterology,[4] in which a group from Spain looked at gluten immunogenic peptides in the stool and documented that you can actually identify these in the stool. People think that, based on dietary review, they are completely gluten free. That may be something in the future that will give us a very good test, and I am excited about the possibility that we will actually be able to detect gluten immunogenic peptides in the stool and know that the patient is still being exposed, as opposed to relying on dietary review, symptoms, and TTG testing.

Dr Balistreri: Thank you. Alessio, final comment?

Dr Fasano: To echo what Ivor has said, we do have a concern. The same Spanish group presented a follow-up of evidence of the robust performance of this test for immunogenic peptides in stool at the World Congress in Montreal.[5] I am as impressed as Ivor that this might be a very objective, strong way to monitor for inadvertent exposure to gluten. There is also a strong effort to develop devices to check for possible cross-contamination in food when people dine out. The Massachusetts Institute of Technology devised a microchip that is quite interesting.[6] I have mixed feelings about having to sit and wait for 10 minutes before figuring out if your restaurant meal is safe for you to eat. If they can bring that down to real time, I believe it would be a major advance. Of course, inadvertent cross-contamination does not occur at home. People know what they are doing. The problem is when you go out to eat. Some restaurants that offer gluten-free meals may not be as careful as they should be because this is now perceived to be a fad, and they do not understand that this is a medical necessity for these people.

Dr Balistreri: Thank you. On behalf of Medscape, I want to thank Dr Hill, Dr Fasano, and all of you for joining us.


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