Duodenal bulb biopsies for celiac diagnosis often unreadable, misleading

Last Updated: 2016-01-13

By Anne Harding

NEW YORK (Reuters Health) - Caution should be used in both acquiring and interpreting duodenal bulb biopsies for the diagnosis of celiac disease in children, according to a new prospective study.

Forty-five percent of bulb specimens were not adequate for morphometric measurement, Dr. Markku Maki, of the University of Tampere School of Medicine in Finland, and colleagues found, while some samples from children without celiac disease had celiac-type pathology. They reported their findings online January 5 in the American Journal of Gastroenterology.

"If bulb biopsies are used, everything must be done with caution, and those who read it should know what they do," Dr. Maki told Reuters Health in a telephone interview. He noted that samples must include longitudinally cut crypts in order to be read morphometrically, which requires that biopsies be cut perpendicular to the luminal surface.

In the past, Dr. Maki and his team write, diagnostic biopsies have been taken from the distal duodenum, but new research has suggested that some patients may have villous atrophy with crypt hyperplasia in the bulb only. Based on this, some new guidelines state that biopsies for diagnosing celiac disease should be taken from the bulb alone.

But several factors make this difficult, the researchers add, including the fact that bulb tissue is hard, making it difficult to take adequate forceps specimens. Brunner's glands and lymphoid follicles in the bulb can also distort the appearance of the villi, they note, while the bulb's high gastric acid load may cause difficulties in diagnosis.

In a 2013 study published in PLoS ONE, Dr. Maki and his team reported on a validation study of their standardized operating procedure (SOP) for morphometric analysis of small intestinal biopsies of adults with and without celiac disease.

In the new study, the researchers used their SOP to evaluate villous height-to-crypt depth ratio (VH:CrD) in 22 children with celiac disease and 22 non-celiac-disease controls. They also analyzed the samples for immunoglobulin A (IgA) deposits targeting mucosal extracellular transglutaminase 2 (TG2).

Twenty of the 45 samples could not be used for morphometric measurement, even after recutting, because they did not include any longitudinally cut crypts. The mean VH:CrD was 0.2 for the celiac disease patients with adequate biopsies. (A ratio of 2.0 or higher is considered normal.) However, 10 of the 13 control patients had injured bulb mucosal lining, with a mean VH:CrD of 1.3. The 2.0 cutoff had a sensitivity of 100% but a specificity of 23%.

The 20 celiac disease patients with frozen tissue samples available had moderate-to-strong deposits of IgA targeting TG2 in bulb tissues, while no such IgA deposits were found in the 17 control patients with samples available.

"The present results confirm that the anatomical bulb must be interpreted with caution, as mucosal inflammation, crypt hyperplasia, and even villous atrophy are common irrespective of the offending agent," Dr. Maki and colleagues write.

"Therefore, routine histologic evaluations of anatomic bulb specimens are not per se sufficient in celiac diagnostics." However, they add, IgA deposits targeting extracellular TG2 within the bulb "proved to be a strong tool in grouping patients correctly."

Several organizations supported this research. The authors reported no disclosures.

SOURCE: http://bit.ly/1PrzqXh

Am J Gastroenterol 2016.