Celiac Disease: Don't Miss This Diagnosis

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Today, I want to talk to you about a condition that you should be thinking about, if not daily, regularly when you're screening your patients for a variety of conditions. That condition is celiac disease. As you know, this is a wheat allergy (a gluten protein that patients are not able to handle well in their small bowels), and it acts as an immune stimulator. Basically there are a number of things that can go awry and lead to atrophic changes in the small bowel, and a variety of malabsorption disorders.

The typical patient would come in with diarrhea or malabsorption, and you would think about celiac disease, particularly in your evaluation of that patient. But a host of patients out there are being missed, because there's a spectrum of disease. There's a mild spectrum, there's a severe spectrum, and then there is a gray zone in between. So I wanted to get you to think about expanding this horizon.

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We do know that celiac disease has a high correlation with a couple of other diseases. In particular celiac disease is often linked with diabetes, and there's a tremendous overlap with dermatitis herpetiformis. Vesicular eruptions on the extensor surfaces of the arms are another very common overlap. Immunoglobulin (Ig) A deficiency also commonly overlaps with celiac sprue. So you should be thinking about celiac disease in a host of patients.

I see celiac disease very commonly in patients when they present with iron deficiency with no other explanation. Vitamin D deficiency is another common condition. So think about this as you start to expand your horizons for testing.

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Primarily, serology includes a test called a tissue transglutaminase (tTG), which has been the standard test, and which is highly sensitive. Testing also includes antiendomysial antibodies and antigliadin antibodies, although antigliadin antibodies are not standard anymore. These antibodies tend to not be very predictive, not very highly sensitive, and not very highly specific.

There is a new test called a deamidated gliadin peptide (DGP), which has just been reported in a very recent article in Alimentary Pharmacology & Therapeutics,^[1] that showed that there was a high sensitivity and specificity using the DGP. This is a test that may or may not be available in your area.

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The most recent report suggested that DGP was helpful in elderly patients who otherwise tested normal on standard tests, the antiendomysial antibodies, and the tTG. Those tests, which would have been our standard, would have potentially missed a sizeable percentage of patients, in particular the older patients presenting with celiac disease. So the DGP may be another test to ask for as you start to expand your horizons.

Duodenal biopsy. Now if the antibody tests are positive, what should you do? You should get a small bowel biopsy. If the patient has classic celiac disease, or they've got dermatitis herpetiformis, and high-profile antibodies, I probably would still obtain the biopsy, but you wouldn't have to. However, I feel a small bowel biopsy is the diagnostic gold standard. Your endoscopists need to be aware that this could be patchy; they need to do a minimum of 4 biopsies to have the high sensitivity that you would need to detect celiac disease. If you do fewer than that, your sensitivity goes down to 90%. So 4 or more biopsies [are required] and in particular [these should be taken] from the second and third portion of the duodenum.

Now it's very important when you do both the serologic testing as well as the biopsies that the patients haven't been on a gliadin-free diet or a gluten-free diet for a long period of time. For several weeks, a gluten-free diet can actually influence their test to be more normal. And again, you may miss the diagnosis.

If patients have self-selected [their diagnosis], and from whatever research [they have read] they think they may have celiac disease, these patients sometimes come to me and tell me they've been on a gluten-free diet for a while and the testing for those patients may not be appropriate right away. Rather, put them back on their gluten and then retest them. I typically would suggest retesting them in around 2-4 weeks. Four weeks gives you a very good safety net. Two weeks is probably the minimum before you start to retest them, and this includes biopsies.

If the biopsies come back normal, what do you do with that patient? Well, if the patient has not been on a gluten-inclusion diet, I would consider that patient to be still in the gray zone. I would put them back on gluten and retest them with a biopsy. If your biopsies come back negative and the patient has not been excluding gluten, then you can feel pretty comfortable and, in fact, certain that the patient doesn't have celiac disease. So that's the exit from that strategy.

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Biopsies can be falsely positive in gluten enteropathy because they can be patchy with villous changes. You may see this with bacterial overgrowth, you may see it with inflammatory bowel disease, and you may see it with milk allergies. There are a number of things that potentially can give you patchy villous blunting. But the histologic criteria for celiac disease are fairly specific and your pathologist should help you in making the diagnosis. If the serum tests positive, again be aware that there are false positives. If the biopsies are negative, I think you can exit that patient from concern [about celiac disease].

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One of the things that you need to consider if you expand your treatment horizons is the patient who may warrant testing, [for example] a patient who has gaseous bloat and diarrhea, obviously. There are a number of other conditions, such as the patient with diabetes or dermatitis herpetiformis. There are a number of reports talking about patients with migraines and patients who have infertility problems. One of the standard tests that our infertility lab does here at Eastern Virginia is check for celiac disease. So again, [celiac disease is] something that you may want to think about in patients who are presenting with hypogonadism, or in patients who are presenting with osteoporosis that is otherwise unexplained.

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There are a number of things; if you start to look at your patient lists every day, I'll bet you'll find these patients. At least in the differential for these patients, celiac disease should figure as a theoretical concern, if not an absolute concern. And appropriate testing is warranted.

Hopefully this gives you some perspective for the next time you see a patient in whom celiac disease is or should be suspected. Don't forget the patient with elevated liver tests. This is something that we're finding more and more routine in gastroenterology -- patients with an autoimmune-type hepatitis, patients who overlap with primary biliary cirrhosis, and even sclerosing cholangitis.

So [when a patient has] abnormal liver tests, a celiac profile becomes very much of a standard for us once we exclude viral hepatitides, hemochromatosis, Wilson's disease, and those types of things that are standard. We do not forget celiac disease as a newcomer [in patients with] liver test elevation.

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So I'll leave you with some guidance of new information as it relates to celiac disease. Hopefully this will serve you well with your next patient. And I look forward to talking with you again. Thanks for listening.