Screening and Diagnosis of Celiac Diseases

Screening for celiac disease has been recommended for specific risk factors.

The anti-endomysium IgA antibody and anti-tissue transglutaminase IgA antibody tests are highly sensitive and specific in identifying individuals with celiac disease.

The anti-endomysium IgA antibody test is an immunofluorescent technique and is relatively expensive; interpretation is operator dependent and prone to errors so that it has largely been replaced by anti-tissue transglutaminase IgA antibody tests, which are simpler to perform and have similar sensitivity and specificity.

Anti-gliadin IgA and IgG and anti-reticulin IgA antibody tests are no longer recommended tests due to lack of specificity.

The anti-endomysium IgA and anti-tissue transglutaminase IgA antibody test can be falsely negative with IgA deficiency, which is associated with an increased incidence of celiac disease. Measurement of serum IgA concentration is mandatory to assure that false-negative results in IgA-deficient individuals are excluded. If celiac disease is suspected in patients with IgA deficiency, intestinal biopsy may be required. Because screening with antibodies may identify patients without documented celiac disease on biopsy, it is important to set the lower limit of antibody titers high enough to avoid false-positive results.

A. Normal
B. Celiac disease



Small Intestinal Biopsy.
Definitive diagnosis of celiac disease requires small intestinal biopsy, as none of the available serologic tests are 100% reliable. The characteristic histologic changes include partial or total villous atrophy, crypt elongation and decreased villous/crypt ratio, increased number of intraepithelial lymphocytes, intraepithelial lymphocyte mitotic index >0.2%, decreased height of epithelial cells, and loss of nuclear polarity. The mucosal involvement can be patchy, so multiple biopsies must be obtained. The intestinal biopsy–based criteria for diagnosis of celiac disease were published by the European Society of Pediatric Gastroenterology, Hepatology and Nutrition and revised in 1990. According to the revised criteria, children with characteristic histologic features and unequivocal clinical response to gluten withdrawal can be considered definitive for celiac disease. Reversal of positive serologic tests after gluten withdrawal is considered supportive evidence. In children <2 yr of age, milk protein–sensitive enteropathy can produce changes similar to celiac disease; confirmation of diagnosis after a gluten challenge is sometimes required. This necessitates three biopsies: an initial biopsy at presentation, the 2nd to document healing with gluten withdrawal, and the 3rd to show recurrent damage with reintroduction of gluten.