Celiac diagnosis being routinely missed

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A report from Chicago, published on the Gastroenterology and Endoscopy US News site this month claimed that only one out of every three patients who undergo an endoscopy with duodenal biopsy has four or more specimens submitted for analysis, despite the fact that four is the minimum number recommended by the American Gastroenterological Association (AGA). These reported results have been taken from a new report presented at the 2011 Digestive Disease Week meeting that took place in the US in early July 2011. As a result, many cases of celiac disease are likely missed, the investigators concluded.

The study of more than 132,000 patients treated over the past four years showed that only about 35% of all duodenal biopsies met the AGA standard since the guideline was published. Additionally, the diagnosis of celiac disease doubles when four or more specimens are submitted from duodenal biopsy.

“The primary reason to perform duodenal biopsy is to assess for celiac disease, and as celiac disease remains under-diagnosed in the United States, physicians should routinely submit at least four specimens when they perform duodenal biopsy,” said lead author Benjamin Lebwohl, MD, instructor of clinical medicine at the Celiac Disease Center, Columbia University College of Physicians and Surgeons, in New York City.

Most estimates indicate that about 95% of people with celiac disease in the United States are undiagnosed, partly because people do not visit a doctor for their problems and partly because those who do are not always checked for celiac disease. The other contributing factor is that even when people are checked, many cases may be missed.

In 2006, the AGA called for all endoscopists to take four or more specimens during duodenal biopsy to assess for celiac disease (Rostom A et al. Gastroenterology 2006;131:1981-2002). According to the AGA technical review, “mucosal changes can be patchy. Therefore, it is important to take multiple endoscopic biopsy specimens (ideally four to six) from the proximal small intestine.” The report also stated that biopsy specimens should be sufficient sizes, carefully oriented and mounted villous side up to enable cross-sectioning rather than tangential sectioning, which could lead to misleading interpretations.

To assess the importance of adherence to the AGA standard, Dr. Lebwohl and colleagues analyzed the biopsy specimens of patients with no known celiac disease who underwent endoscopy with duodenal biopsy between 2006 and 2009, using a prospectively maintained database of a pathology laboratory that operated in 43 states in the nation. Only 45,995 of more than 132,000 endoscopies met the AGA criteria. Most often, only two specimens were submitted.

Patients were undergoing duodenal biopsy during upper endoscopy for various indications, including suspected celiac disease (80%), anemia (19%), diarrhea (17%) and weight loss (8%). Even among patients whose primary reason for endoscopy was suspected celiac disease, only 38.5% had four or more specimens submitted. Among clinical indications, diarrhea and malabsorption were associated with increased adherence, whereas advanced patient age, dyspepsia and heartburn were associated with decreased adherence.

When four or more specimens were submitted, diagnostic yield improved markedly, with the probability of a new diagnosis increasing from 0.7% to 1.8% (P<0.0001). When the gross appearance of the specimen was abnormal, the association was even more dramatic, increasing odds of diagnosis by more than threefold (odds ratio [OR], 3.67; 95% confidence interval [CI], 2.86-4.72).

“This indicates that the low rates of celiac disease diagnosis in this country may be due in part to endoscopist-related factors. Increasing the number of specimens submitted during duodenal biopsy appears to be an effective way to diagnose more of these patients,” said Dr. Lebwohl, adding that it takes only an extra minute to double the number of specimens from two to four.
“However, most likely the low adherence is due to a lack of awareness among physicians, not time constraints. The recommendation is recent and perhaps it will take time for this practice to gain widespread approval,” he added.

Retrieval rates are improving, the study showed. Adherence with this criterion increased from 33.8% in 2006 to 37.2% in 2009 (P<0.0001). However, that still falls short of what’s recommended, said Dr. Lebwohl.

Many studies published in the past four years also demonstrate that retrieving four to six specimens from different areas of the duodenum offers the best chance for an accurate diagnosis of celiac disease (Green PH, Cellier C. N Engl J Med 2007;357:1731-1743; Hopper AD et al. Endoscopy 2008;40:219-224). In a Canadian study of 247 patients, researchers found that taking only two biopsy specimens led to a confirmed diagnosis of celiac disease in 90% patients; but for 100% confidence in diagnosis of celiac disease, four duodenal biopsy specimens should be retrieved, the researchers concluded (Pais WP et al. Gastrointest Endosc 2008;67:1082-1087).

Recently, experts called on endoscopists to ensure they spread their biopsy specimens throughout the duodenum, in addition to taking multiple specimens (Webb C et al. J Pediatr Gastroenterol Nutr 2011;52:549-553).

“The standard really should be a minimum of four to six specimens, taken from the second and third parts of the duodenum, as well as the duodenal bulb. Unfortunately, that’s not quite the standard of what’s being done,” said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia School of Medicine, in Norfolk.

Dr. Johnson said low adherence rates reflect a lack of awareness about recommendations, as well as a failure on the part of physicians to understand the protean nature of this disease.

“Hopefully, this study will help reiterate that message [about increased biopsy specimens] and improve the treatment of what is a fairly prevalent disease in the United States,” said Dr. Johnson, who is a past president of the American College of Gastroenterology.