Many people have gluten intolerance yet still test negative for celiac disease. What symptoms should I look for in gluten- intolerant patients? Will a gluten-elimination diet help diagnose patients with unusual symptoms?
—MISTI KONSAVAGE, PA, Burkesville, Ky.

First, it is important to maintain a broad differential. Keep asking questions and pursuing alternative diagnoses when the puzzle pieces refuse to fit together. Does the patient really have gluten enteropathy? Or could this be a case of lactose intolerance, Crohn’s disease, giardiasis, or even malignancy?

Second, precisely which tests were negative? Serologic tests only or small-bowel biopsy? The number and complexity of tests that can be ordered—from tissue transglutaminase and immunoglobulin A-class endomysial autoantibodies to HLA haplotypes—has increased significantly over the years. Since these tests are both expensive and imperfect, I never order or interpret them without the help of a gastroenterologist.

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I would also want to know whether or not the tests were done after a gluten-free diet had already been instituted. This can give rise to falsely negative blood tests in as few as four weeks after the diet was started.

Finally, experts concede that there may exist a subset of patients—albeit a very small one—who have negative serologic and histologic evaluations but seem to respond to a gluten-free diet. In such cases, it is important to treat the patient and not the laboratory tests while remaining alert for new clinical or laboratory evidence that might eventually clarify the diagnosis.
—Reuben Zimmerman, RPA-C