Number of Endoscopic Biopsy Specimens Needed to Confirm a Diagnosis of Celiac Disease

David A. Johnson, MD, FACG, FACP


August 06, 2008

How Many Duodenal Biopsy Specimens Are Required to Make a Diagnosis of Celiac Disease?

Pais WP, Duerksen DH, Pettigrew NM, Bernstein CN
Gatrointest Endosc. 2008;67:1082-1087


Celiac disease, a prevalent food hypersensitivity disorder, is an autoimmune disorder of the small intestine that occurs in genetically predisposed individuals and results in a small intestinal inflammatory reaction to gluten proteins (wheat, barley, rye). The prevalence of celiac disease in the United States is estimated to be approximately 1/133.[1] Although diarrhea is the more classic presentation, the manifestations may be quite protean (eg, abdominal pain, bloating, weakness, iron deficiency, osteoporosis).

Serologic testing is quite helpful in screening patients for this immune-mediated enteropathy, but histologic confirmation with duodenal biopsies remains the gold standard for diagnosis. However, there may be patchy distribution of duodenal villous atrophy and there is no clear consensus on the number of biopsies needed to establish or exclude the diagnosis. Although at present there are no specific recommendations from the pediatric gastroenterology guidelines, the American Gastroenterological Association recommends that ideally 6 distal duodenal biopsy specimens should be obtained.[2]

There is variability in the degree of mucosal damage in celiac disease. The first phase is an infiltration with increased numbers of intraepithelial lymphocytes. The second phase is hyperplastic with crypt hypertrophy. The third phase is destructive, with crypt atrophy.

This retrospective study from a tertiary university hospital involved a medical record audit and histology slide analysis of 247 cases of patients who underwent endoscopy to confirm the diagnosis of celiac disease. The final diagnosis was established after a chart review with consideration of clinical symptoms, signs, serologic testing, and histologic analysis of biopsies of the duodenum. All biopsies were evaluated by a single investigator and in cases of uncertainty, consensus was reached through a process review with a second investigator. Serologic testing was not available in all patients.

The diagnosis of celiac disease could be confirmed if only 2 biopsies were taken in 90% of patients. Incremental biopsies showed increased sensitivity: 3 biopsy specimens (diagnosis could be confirmed in 95% of patients) and 4 biopsy specimens (diagnosis could be confirmed in 100% of patients). The site of biopsy (second, third, or fourth portions of duodenum) had no influence on outcome. Histologic variability among duodenal biopsies was evident in 25% of cases.


The clinical take-home message from this study is clear: These data suggest that 4 random biopsies should be taken to confirm the diagnosis of celiac disease. Given the variability in sensitivity and specificity of serologic testing, adequate biopsies should be taken from all patients in whom the diagnosis of celiac disease is considered. To prove this strategy absolutely, a prospective trial would be necessary to confirm or refute the diagnosis. However, at present, on the basis of these findings, I would suggest the new "gold standard" for the diagnosis of celiac disease should be as outlined in this report.



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