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Diagnose Celiac Disease

The American Gastroentereological Association (AGA) Institute published its recommendations on the diagnosis and management of celiac disease in Gastroenterology 2006;131:1977-1980.  The following is a summary of those recommendations; the complete AGA medical position statement can be found at

Subsequently, the National Guideline Clearinghouse (NGC) Guideline Sythesis on the Diagnosis and Management of Celiac Disease was published in April 2010.
This document provides a direct comparison of the recommendations presented in the following guidelines: American Dietetic Association 2009 (ADA), American Gastroenterological Association Institute 2006 (AGA), National Institute for Health and Clinical Excellence 2009 (NICE), and the World Gastroenterology Organization 2007 (WGO-OMGE).

Finally, the American College of Gastroenterology (ACG) issued the ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease in the May 2013 issue of Am J Gastroenterol 2013;108:656-676. The document can be found online on the ACG website: 

The prevalence of celiac disease in the general United States population is approximately 1%-2%.  Celiac disease may present at any age, in either sex, and with a wide variety of clinical symptoms.  High risk populations include:

  • first-degree and second-degree relatives of patients with celiac disease;
  • patients with iron deficiency anemia (IDA);
  • patients with osteoporosis and bone demineralization;
  • patients with Type 1 diabetes mellitus (IDDM);
  • patients with liver disease;
  • patients with genetic disorders, such as Down syndrome and Turner syndrome;
  • patients with autoimmune thyroid disease;
  • patients with reproductive disorders; and
  • patients with other diseases, such as Addison disease, immunoglobulin A nephropathy, idiopathic epilepsy, occipital calcifications, Sjögren syndrome, and ataxia.

The AGA Institute recommends testing for celiac disease in symptomatic individuals who are at high risk, including those with unexplained iron deficiency anemia, a premature onset of osteoporosis, Down syndrome, unexplained elevations in liver transaminase levels, primary biliary cirrhosis, and autoimmune hepatitis. It recommends that testing for celiac disease should be considered, especially if symptoms that could be the result of celiac disease are present, in patients with Type 1 diabetes, autoimmune thyroid disease, Sjögren syndrome, unexplained recurrent fetal loss, unexplained delayed puberty, selective IgA deficiency, irritable bowel syndrome, Turner syndrome, peripheral neuropathy, cerebellar ataxia, and recurrent migraine, as well as children with short stature and first- and second-degree relatives of patients with celiac disease.

Diagnostic testing for celiac disease must be performed prior to removing gluten from the patient’s diet, since both serological and histological evidence of celiac disease may resolve with elimination of gluten from the diet.

Serologic Testing

Serologic tests for IgA anti-endomysial antibody (EMA) and IgA tTGA are sensitive and specific for the detection of celiac disease.  These tests have supplanted the use of gliadin antibody testing as the preferred means of serologic detection.  The specificity of the IgA tTGA assay is > 95% and it has a sensitivity in the range of 90–96%. The EMA test is an indirect immunofluorescence assay, and it has a slightly lower and variable sensitivity, but an excellent specificity (99.6%).

The 2006 AGA Institute recommendations note that the prevalence of IgA deficiency in celiac disease is low enough that the routine measurement of serum IgA levels, along with IgA EMA or tTGA, is not warranted as a first step toward diagnosis of celiac disease unless IgA deficiency is strongly suspected.  In cases of selective IgA deficiency, the IgG EMA and/or IgG tTGA tests have excellent sensitivity and specificity, although these IgG-based assays are less sensitive and specific than the IgA-based tests in those with normal levels of IgA. Measurement of the serum IgA level is recommended in individuals with a negative IgA EMA or IgA tTGA in whom celiac disease is still suspected.

If celiac disease is strongly suspected despite negative serologic test results, one can test for the presence of the disease-associated HLA alleles and, if present, proceed to small intestinal mucosal biopsy. Alternatively, it is reasonable to proceed directly to upper intestinal endoscopy and small bowel biopsy if the signs and symptoms that suggested celiac disease would otherwise warrant those procedures.

Histological Testing

While positive serologic test results are considered supportive of the diagnosis of celiac disease, the “gold standard” for establishing the diagnosis remains the finding of histologic changes in the small intestinal mucosa from a distal duodenal biopsy specimen.  These changes can range from total to partial villus atrophy, and crypt lengthening with an increase in lamina propria and intraepithelial lymphocytes.  An increase in intraepithelial lymphocytes without other mucosal changes may represent latent celiac disease, or a part of the spectrum of gluten-sensitive enteropathy, but should not be considered diagnostic of celiac disease.

Multiple biopsy specimens should be taken from the second part of the duodenum or beyond.  Patients should undergo biopsy soon after obtaining positive serological results and should not avoid gluten until after biopsy specimens are taken, since a gluten-reduced diet can reduce the severity of lesions and impact pathological readings.  If patients are already on a gluten-free diet, a 4-week or greater gluten challenge with sufficient gluten to cause symptoms prior to conducting the biopsy is typically sufficient.

HLA-DQ2 and -DQ8 Testing

Although the prevalence of the HLA class II heterodimers HLA-DQ2 and HLA-DQ8 is 40% in the general US population, it is virtually 100% in patients with celiac disease.  Therefore, the absence of these alleles can exclude celiac disease as a diagnosis when results from other tests are not clear.  However, only 3%-5% of HLA-DQ2 or HLA-DQ8 subjects will have celiac disease.

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