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Thursday, February 10, 2011
Making a Diagnosis of Celiac Disease Can Be Tricky
This article is from last month, but I thought it was worth sharing with my readers.

Making a Diagnosis of Celiac Disease Can Be Tricky : Internal Medicine News

By: LAIRD HARRISON, Internal Medicine News Digital Network
01/12/11

LAS VEGAS – New testing protocols are helping clinicians with the challenging diagnosis of celiac disease, according to Dr. Ivor D. Hill, a professor of pediatrics at Wake Forest University, Winston-Salem, N.C.

While the only treatment for celiac disease is a gluten-free diet, Dr. Hill said, the diet is expensive and imposes social costs, so it should not be prescribed lightly. "Confirm before you treat," he said.

Researchers believe the disease affects about 1% of the population. "You can expect to see 5-20 affected children in an average pediatric practice," Dr. Hill said at a pediatric update sponsored by the American Academy of Pediatrics California District 9.

Among the symptoms in young children are failure to grow, diarrhea, bloating, flatulence, abdominal distension, and transaminitis.

In older children, the symptoms are often milder and can vary tremendously. In addition to having gastrointestinal symptoms, some patients have dermatitis herpetiformis characterized by papules on the elbows, buttocks, or knees. About 10% are short of stature. Iron-deficient anemia, rickets, arthritis, neuropathy, ataxia, and other neurological symptoms all can be manifestations of celiac disease. Many children are irritable. Poor dental enamel formation that looks similar to fluorosis or tetracycline staining also can be signs of celiac disease.

Some people with the syndrome are totally asymptomatic.

Autoimmune diseases, including type 1 diabetes, thyroiditis, autoimmune hepatitis, Sjögren's syndrome, and arthritis are associated with an increased risk of celiac disease. So is IgA deficiency; a family history of celiac disease; and Down, Turner, and Williams syndromes. Whether to screen these or any other individuals for celiac disease if they are not symptomatic, is controversial.

"When it comes to symptomatic patients, there is a consensus," said Dr. Hill. "There’s a difference of opinion on testing asymptomatic patients."

In patients with typical gastrointestinal symptoms, begin with the serologic tests. While tests for the antigliadin antibody (AGA) IgG and IgA are inexpensive and easy to perform, they have low sensitivity and specificity. By contrast, the test for the IgA endomysial antibody (EMA) has high sensitivity and specificity, but is expensive, time consuming, operator dependent, and of no use in IgA-deficient patients.

Testing for IgA anti-tissue transglutaminase (TTG), on the other hand, is easier and less expensive than testing for EMA, and newer versions are now considered as sensitive and specific as EMA. But it is also of no use in the case of IgA deficiency.

A new version of the antigliadin test, using deamidated gliadin antibodies, has shown much higher sensitivity and specificity than the AGA test in recent studies (Dig. Dis. Sci. 2008;53:1582-8), but this test is still not as good as the TTG or the EMA tests, said Dr. Hill.

So he advocated a combination of TTG and serum IgA level, although EMA may work better in diabetics. There is no benefit to a panel of tests, he said.

However, he warned that all these tests are less accurate in the real world than in the laboratory. And sensitivity declines in children less than 2 years of age, so combining TTG with the newer deamidated gliadin tests might be warranted in this young age group.

If these tests are positive, proceed to biopsies, Dr. Hill recommended. Clinicians should also consider biopsies if the tests are negative but they strongly suspect celiac disease.

Another key element in diagnosing celiac disease is that patients with the syndrome will improve on a gluten-free diet. And this diet is the standard treatment. But some other possibilities have appeared on the horizon. "It’s exciting," said Dr. Hill.

Intraluminal approaches include modification of wheat protein or transamidation of wheat flour. "It’s looking promising but hasn’t been confirmed yet," said Dr. Hill.

Several digestive enzymes have been developed with the intention of digesting the proteins before they can be taken up by the intestinal mucosa. Peptide-binding agents also are being tested to prevent the proteins from reaching the mucosa.

Biological antagonists include a zonulin inhibitor, TTG inhibitors, cytokine inhibitors, and DQ2 and DQ8 inhibitors. A vaccine is in the works as well. In addition, the timing of the introduction of gluten might be manipulated to build up tolerance.

These approaches are not yet ready for prime time, leaving diet as the primary treatment. But many patients find it hard to stick to the diet. Dr. Hill advocated a self-administered questionnaire, or better yet, assessment by a trained interviewer, as well as continued monitoring through TTG testing at 3 months, 6 months, 12 months, and then annually, combined with a dietary review, to see how well the patient is adhering to the diet. Repeat biopsies should be done only in select cases.

Dr. Hill disclosed that he is a consultant to AstraZeneca.

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