Brian Lacy, MD, and Benjamin Lebwohl, MD, on Testing and Biopsy for Celiac Disease

Dr Lacy and Dr Lebwohl continue their discussion on celiac disease, focusing on testing and biopsy to confirm the diagnosis.

Listen to the first podcast in this series here:

Brian Lacy, MD, is a professor of medicine and gastroenterologist at Mayo Clinic Jacksonville, and Section Editor for Stomach and Small Bowel Disorders for the Gastroenterology Learning Network. Benjamin Lebwohl, MD, is the Louis and Gloria Flanzer Scholar, an associate professor of medicine, and director of the Celiac Disease Research Center at Columbia University Medical Center in New York.

TRANSCRIPT:

Rebecca Mashaw:  Welcome to another podcast from the Gastroenterology Learning Network. I’m your moderator, Rebecca Mashaw. Thank you for joining us for this continuation of a conversation on celiac disease with doctors Brian Lacy and Ben Lebwohl.

Dr Lacy: Hi, I’m Brian Lacy, professor of medicine at the Mayo Clinic in Jacksonville, Florida. I’m continuing my conversation on celiac disease with Dr Ben Lebwohl, associate professor of medicine and director of the Celiac Disease Research Center at Columbia University in New York City.

Ben, in our first podcast, you gave us an overview of celiac disease. Today, I’d like to talk about diagnosing celiac disease through testing and biopsies. For the clinician in a busy practice, what's the most effective and efficient means of testing for celiac disease?

Dr Lebwohl:  Testing for celiac disease typically begins with checking serologies. If you only remember one serology for celiac disease, it's tissue transglutaminase, tTG-IgA. It has very high both sensitivity and specificity. Both are in the 90s. You'll catch most patients, and you will not have too many false positives.

Now, we all are familiar with the idea of celiac panels. Sometimes, that can actually cause more confusion than clarity. The reason panels exist in celiac disease is because no one serology is perfect. The tTG-IgA, that's your desert-island test. That's the one that you want to remember, but you will miss a patient, for example, with selective IgA deficiency.

Typically, a panel will include both a tTG-IgA and a total IgA. If the total IgA is low or undetectable, and you're dealing with a patient with selective IgA deficiency, then there's a role for other serologies, the IgG serologies. There is a tTG-IgG, it's far less specific, far more prone to false positives.

There's also a set of deamidated gliadin antibodies. The deamidated gliadin antibodies or DPG IgG is our go-to serology in someone with selective IgA deficiency.

Going back to your question about what's the convenient or most effective and efficient way of testing for celiac disease, a tTG-IgA. One test and you'll catch the great majority of your patients that way.

Dr Lacy:  Great teaching point. Thank you. Ben, you briefly mentioned the genetic predisposition for celiac disease. When do you decide to do genetic testing for celiac disease? Are there any special rules about those genetic tests that we should be aware of?

Dr Lebwohl:  There are 3 main scenarios were testing for the celiac genes, HLA-DQ2/DQ8, can be helpful. One is a situation where you have a discrepancy between one's serologies and one's biopsy, either they have duodenal villous atrophy. It looks like celiac disease, but their serology is just not showing an elevated TTG. A genetic test may be helpful in helping change our sense of the likelihood that this really is celiac disease.

A second context is when assessing relatives, especially young children. Someone's mother/father has celiac disease, you're dealing with an infant, and you want to know, "Will this person ever be at risk for celiac disease?"

If the DQ2 or DQ8 are absent, this person tests negative for both, that person's lifetime risk of getting celiac disease is close to zero because we see those genes as necessary for developing celiac disease -- necessary but insufficient.

Discrepancy between serology and biopsy, assessing a relative about what is their lifetime risk, "Will they ever get celiac disease?" Then the third scenario, the increasingly common scenario, where someone comes to the doctor already having started a gluten-free diet, because once the gluten-free diet is started, the clock starts ticking.

If that person had celiac disease, things will normalize. Their antibodies will go towards normal over the course typically of months. Their duodenal biopsy may even normalize over time on a strict gluten-free diet, but their genes don't change.

Testing for DQ2 and DQ8 in that context might be very helpful because if they don't have the DQ2 or DQ8 gene, that person does not have celiac disease. We don't have to really think about doing a gluten challenge, for example, in that situation. Those are the three main clinical scenarios where genetic testing is indicated and helpful.

Dr Lacy:  Ben, those are three great roles to remember. Thank you. You mentioned duodenal biopsy. This is still a controversial topic. When do you do it, and how should it be done?

Dr Lebwohl:  As the serologies have gotten better and that tTG-IgA serology has a sensitivity of perhaps 90 percent of specificity, 98% or higher -- in other words, a positive tTG, especially a highly elevated tTG -- it's highly likely to mean celiac disease. Doctors and patients are asking, "Why even bother to do the duodenal biopsy?"

In fact, European guidelines for children have allowed for a biopsy-free approach in certain scenarios if you have a sufficiently elevated tTG, greater than 10 times the upper limit of normal in someone with a compatible HLA type and with a secondary test that's also positive, typically the anti-endomysial antibody, one that's more commonly performed in children than adults.

In that situation where the positive predictive value for celiac disease is close to 100%, the biopsy could potentially be skipped. These guidelines have not made their way across the Atlantic to the US guidelines, either in children or in adults.

It should be pointed out there are no guidelines of major professional organizations that say skipping the biopsy is OK in adults, primarily because the positive predictive value for even a highly elevated tTG-IgA has not been shown to be close enough to 100% in adults to justify skipping that biopsy.

Actually, a recent multicenter study looking at multiple different countries and endoscopy suites to tTG assays found that a high enough tTG elevation -- greater than 10 times the upper limit of normal -- gives you 95% positive predictive value for celiac disease.

That sounds great, but that's to me unacceptably low when you're prescribing a lifelong diet that can be difficult, expensive, socially isolating, and has a number of downsides. For now, at least among adults, the biopsy is a central part of the diagnosis of celiac disease.

There are exceptions and someone who's unwilling or unable to tolerate a duodenal biopsy. Whether it's because they've multiple comorbidities that may interfere with sedating the patient, or for example, they have a bleeding disorder that makes a biopsy unacceptably hazardous, we borrow those pediatric guidelines.

Even so, there's always that little asterisk. We say that they were diagnosed based on highly elevated serologies. We're pretty sure they have celiac disease. It still appears to be the case that the biopsy is the way we firm up the diagnosis. In those exceptions, we sometimes rely on things like capsule endoscopy to bolster our confidence even further if we're missing tissue diagnosis.

Dr Lacy:  Wonderful. Thanks for this great discussion today, Ben, and I look forward to our next conversation on this important topic.

Rebecca Mashaw: Thank you for joining us today, and be sure to look for the next podcast in the series, which in Drs Lacy and Lebwohl will discuss the challenges and the importance of a gluten-free diet for patients with celiac disease.