College of American Pathologists
Printable Version

  Laboratory diagnosis
  of celiac disease


cap today

November 2005

Feature Story

CAP TODAY published an article in November 2000 about Nancy Cornish, MD, director of microbiology, Methodist Hospital and Children’s Hospital, Omaha, who is working to improve physician test-ordering. She teaches Methodist’s physicians about lab tests through periodic clinical briefs, which she writes and distributes. The response of CAP TODAY readers to Dr. Cornish’s work was so enthusiastic and the requests for copies of her briefs so numerous that we asked her to share the clinical briefs she writes as they become available. Here, this month, is her word on celiac disease.

New consensus guidelines from the National Institutes of Health recommend serologic screening and, if positive, confirmation with small bowel biopsy. Based on these recommendations, the laboratory now offers a celiac disease reflexive panel that provides sensitive, specific, cost-effective serologic testing in patients clinically suspected to have celiac disease.

Celiac disease and dermatitis herpetiformis, a skin disease, the two forms of gluten-sensitive enteropathy (GSE), are characterized by intolerance to gluten, the protein of wheat, rye, and barley. Classic celiac disease in adults is characterized by gastrointestinal complaints and changes secondary to malabsorption caused by immune-mediated injury of the small bowel. Symptoms may include abdominal discomfort, diarrhea, flatulence, bloating, steatorrhea, weight loss, fatigue, and malaise. Other people may have atypical, silent, or latent celiac disease.2 All GSE patients have an increased risk of lymphoma. Symptoms and risk of lymphoma may be reduced by placing patient on a gluten-free diet.

  • Accurate diagnosis of celiac disease requires that patients have gluten in their diet at the time of testing.
  • A diagnosis of celiac disease should not be made on the basis of positive serological tests alone. Multiple small bowel biopsies from the second part of the duodenum or beyond are needed to confirm the diagnosis. The only exception to this rule is if the patient has biopsy-proven dermatitis herpetiformis.
  • Antigliadin antibodies are no longer recommended as a routine screening test because of variable sensitivity and specificity, except in young children where they may be used as an adjunctive test.
  • There is no advantage to using a panel of tests incorporating gliadin, endomysial, and tissue transglutaminase IgA over a single test detecting either tissue transglutaminase or endomysial antibodies.
  • Detection of tissue transglutaminase antibody or endomysium antibody are both highly sensitive and specific. However, the tissue transglutaminase antibody test is more sensitive, easier to perform, and more reproducible. The sensitivity is 95 percent to 98 percent and the specificity is 94 percent to 95 percent.
  • A positive serological test with a small bowel biopsy diagnostic of celiac disease or skin biopsy-proven dermatitis herpetiformis in a patient with gluten in his or her diet allows a presumptive diagnosis of celiac disease. A definitive diagnosis is provided by resolution of symptoms following the introduction and maintenance of a strictly gluten-free diet.
  • When patients successfully maintain a gluten-free diet, tTG IgA antibodies disappear from serum. Endomysial IgA titers may be ordered, if needed, to monitor adherence to diet.
  • High-risk populations that should be screened for celiac disease include those with symptoms, individuals with auto immune disorders, (for example, type 1 diabetes mellitus, thyroid, adrenal, liver, and Sjögren’s syndrome), and first- and second-degree relatives of patients with celiac disease. Screening of the general population is not recommended at this time.
  • Two percent of patients with celiac disease will be IgA deficient and unable to make IgA antibodies. These patients need to be screened using an IgG test. (Reflex Algorithm.)
  • Tests may be ordered separately if you prefer.
  • When the diagnosis is uncertain due to indeterminate results, then genetic markers (HLA DQ typing) may be of benefit.


1. Rostom A. Celiac Disease Summary, Evidence Report/Technology Assessment No. 104. AHRQ Publication No. 04-E029-1, Agency for Healthcare Research and Quality, June 2004/

2. Nimmo M. Celiac disease: an update with emphasis on diagnostic considerations. Laboratory Medicine. 2005; 36(6): 366–369.