The Challenge of Celiac Disease Diagnosis


Celiac disease is an autoimmune disorder where the ingestion of gluten leads to damage in the small intestine. According to the Celiac Disease Foundation, it is estimated to affect 1 in 100 people worldwide, and approximately 2.5 million Americans are undiagnosed and are at risk for long-term health complications. Establishing an accurate diagnosis is critical for improved quality of life and prevention of associated side effects. Unfortunately, celiac disease is a challenge to diagnose.

Mayo Clinic researchers conducted a thorough review to examine diagnostic testing strategies for celiac disease, focusing on published guidelines, for the evaluation of patients with suspected celiac disease. The review was published in the Expert Review of Clinical Immunology.

Numerous guidelines and practice parameters related to celiac disease have been published by different professional organizations. Most of these guidelines include recommendations for testing in the context of celiac disease diagnosis. However, the guidelines often contradict one another.

Melissa Snyder, Ph.D.
Melissa Snyder, Ph.D.

“Unfortunately, there are often significant differences in the recommendations of the various guidelines, which can lead to confusion among clinicians,” said Melissa Snyder, Ph.D., Consultant of Clinical Biochemistry at Mayo Clinic and first author on this review. “We hoped with this review to summarize the similarities and differences in the published guidelines, and to provide a better understanding of the laboratory testing available for celiac disease.”

Celiac disease is challenging to diagnose because of its wide variety of clinical symptoms, making identification of patients truly needing to be tested difficult. Further, the awareness of celiac disease in the general population has dramatically increased, resulting in many patients requesting testing or even self-diagnosing.

“Patients may present to their physician and request testing because they are convinced their symptoms are due to celiac disease. Other patients may pre-emptively initiate “self-treatment” with a gluten-free diet, which complicates the diagnostic testing for celiac disease,” said Dr. Snyder.

Celiac disease evaluation is also challenging to diagnose due to the number of diagnostic tests available. Laboratories offer an array of antibody serology tests, along with genetic testing options. The selection of which are the most appropriate tests for a given patient can be difficult. In this review, Mayo Clinic researchers focused primarily on serology and genetic testing to diagnose celiac disease, along with biopsy.

The review indicated that most of the published guidelines agreed that anti-tissue transglutaminase (TTG) antibody IgA is the most useful initial test for the evaluation of patients with suspected celiac disease. The guidelines differed slightly in terms of which patients should be tested for celiac disease and which tests, if any, should be used in conjunction with or as confirmation for TTG-IgA.

“The most significant difference between the guidelines is the recommendation of whether or not a small intestinal biopsy is needed if the antibody serology, specifically TTG-IgA, is positive. Because a biopsy is an invasive and expensive procedure, there is a push to rely only on serology for the diagnosis. However, studies that address this option are not conclusive, and for most patients, a biopsy still likely provides important information for clinical management,” added Dr. Snyder.

These findings are significant and will assist other physicians in understanding the differences in published guidelines for the diagnosis of celiac disease, and why these differences exist. They may also help physicians in selecting the most appropriate testing for their patients.

“There is likely not a one-size-fits-all approach to diagnostic testing for celiac disease. Although we want to standardize the testing as much as possible, different approaches may be needed, depending on the characteristics of the patient being evaluated,” said Dr. Snyder. “Ultimately, a better understanding the testing options available will lead to improved utilization and accuracy for the diagnosis of this disease.”

For more information about testing for celiac disease, view Mayo Medical Laboratories’ comprehensive test offering.






Kelley Luedke (@kschrib)

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.