Approximately 2 million people in the United States have celiac disease, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Many in this population suffer symptoms but remain undiagnosed due to the difficulty in recognizing the disease. Recently, a group of researchers in the United Kingdom developed and evaluated a decision tool based on severity of symptoms and results of a blood test that can aid doctors in the diagnosis of the disease. Using the tool, physicians may decide with more confidence whether to recommend their patients undergo an intestinal biopsy, currently the gold-standard for celiac disease diagnosis. They can recommend that those with high-risk symptoms and positive lab test results undergo biopsy for a definitive diagnosis while those patients with low-risk symptoms and negative blood test results be spared the invasive procedure. These findings were published in the April 2007 issue of the British Medical Journal (BMJ).

Celiac disease is an autoimmune disorder in which antibodies directed against gluten, a substance found in grains such as wheat, rye and barley, cause inflammation and tissue damage in the small intestine. This can lead to problems with the absorption of nutrients in food. Diagnosis can be made difficult by the wide range of signs and symptoms, and by confusing the symptoms with those of other diseases. Although there is no cure for celiac disease, a definitive diagnosis would guide an affected person to avoid the gluten-containing foods that cause the autoimmune response. Those with a negative diagnosis would be free from the restrictive gluten-free diet.

To develop the decision tool, Dr. Andrew Hopper and his colleagues at Royal Hallamshire Hospital, Sheffield, retrospectively evaluated 1464 patients who were referred by their primary doctors to specialists for endoscopy and who had undergone an intestinal biopsy. The researchers categorized patients who presented with weight loss, diarrhea, and anemia as having “high risk” symptoms and all others as having “low risk” symptoms for celiac disease. One hundred nine (109) of these patients were also tested for anti-tissue transglutaminase (anti-tTG), one of the laboratory tests for celiac disease.

Using results from the retrospective study, the scientists designed the clinical decision tool and then tested it on a second group of 2000 patients who had the blood test for anti-tTG and an intestinal biopsy performed. The results from the evaluation of the decision tool were encouraging. No cases of celiac disease were missed in patients with high risk symptoms and positive anti-tTG results (sensitivity of 100%) and all of the patients in the low risk, negative antibody group were also negative for the disease by biopsy. In addition, a majority (58.5%) of the 2000 participants could have been spared the invasive intestinal biopsy had the decision tool been employed, without affecting the number of cases of celiac disease detected.

Combining the criteria of symptoms and blood test results proved useful in the study. However, follow-up testing with a biopsy in some cases may still be important because the tool does have limitations:

High risk symptoms and positive anti-tTG results are not conclusive for celiac disease; 40% of those in this category were negative by biopsy for the disease.

High risk symptoms and negative anti-tTG results are also not conclusive in eliminating concern. A very small percentage (0.4%) of patients in this group was positive for the disease by biopsy.

There is some debate about whether adding a second blood test such as anti-endomysial antibody (EMA) would improve the performance of the diagnostic tool. In addition, as noted in a commentary on the studies in the same issue of BMJ, HLA testing for the genes that code for celiac disease, DQ2 and DQ8, may further improve predictability. The commentary also pointed out that criteria similar to those used in this decision tool are currently used by some physicians in evaluating patients. Therefore, the results of these studies may not change much in the way physicians approach the diagnosis of celiac disease but do confirm the value of using such a tool.

Sources

S1
Hopper A, et al, (April 2007) Pre-endoscopy serological testing for coeliac disease: evaluation of a clinical decision tool. British Medical Journal. Available online, accessed June 2007 at: http://www.bmj.com/cgi/content/full/334/7596/729

S2 Graber M, Kumar A (April 2007) Commentary: Reaching a milestone in diagnosing coeliac disease. British Medical Journal. Available online, accessed June 2007 at: http://www.bmj.com/cgi/content/full/334/7596/732

S3
National Digestive and Diseases Information Clearinghouse. Celiac Disease. Available online, accessed June 2007 at: http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/index.htm