May 03, 2016
2 min read

Ultra-short celiac disease diagnosis may represent early disease, mild clinical phenotype

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A study of the clinical implications and presentation of ultra-short celiac disease, in which villous atrophy is confined to the duodenal bulb, found that the diagnosis may represent early stage or limited celiac disease with a milder clinical phenotype and infrequency of nutritional deficiencies. Moreover, the study found that a single biopsy of the duodenal bulb significantly increases the diagnostic yield for celiac disease.

“We ... aimed to establish the prevalence of USCD in a large patient cohort, in the context of a routine duodenal biopsy strategy in all-comers to open-access diagnostic gastroscopy,” Joseph A. Murray, MD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote. “We aimed to assess the ideal number and site of bulb biopsy for the detection of USCD. Furthermore, we aimed to establish the clinical and histologic phenotype of USCD.”

Joseph A. Murray

Murray and colleagues prospectively recruited 1,378 patients (mean age, 50.3 years; 62% women) who underwent endoscopy at a tertiary medical center in the U.K. from 2008 through 2014, from whom routine duodenal biopsy specimens were collected from the duodenal bulb (D1) and the second part of the duodenum (D2). Within this cohort, they also collected standardized quadrantic D1 biopsy specimens from 181 consecutive patients with a high suspicion of celiac disease (mean age, 46.5 years; 64% women) to determine the ideal number and site for D1 biopsy. Then they compared clinical data between patients diagnosed with USCD, conventional celiac disease and controls, and also compared the number of intraepithelial lymphocytes (IELs) and immune phenotypes between D1 vs. D2 in patients with celiac disease.

Overall, 268 participants were newly diagnosed with celiac disease, 9.7% of whom had villous atrophy confined to D1 and were diagnosed with USCD (P < .0001). Taking an additional D1 biopsy specimen from any D1 site compared with a distal biopsy alone increased the diagnostic yield of celiac disease detection by 9.3% to 10.8% (P < .0001).

Patients with USCD were younger than patients with conventional celiac disease (P = .03), had lower tissue transglutaminase antibody titers than patients with conventional celiac disease (P = .001) and less frequently presented with diarrhea than patients with conventional celiac disease (P < .0001). Ferritin deficiency prevalence was higher in patients with conventional celiac disease vs. USCD and controls (P = .007), as was folate deficiency (P = .003).

Controls had lower median IEL counts in D1 vs. D2 (P = .002), but all counts were below the 25 IEL/100 enterocyte cut-off. Patients with celiac disease had a median IEL count of 50/100 enterocytes in D1 and 48/100 enterocytes in D2 (P = .71), so IELs were immunophenotypically indistinguishable between D1 and D2 in celiac patients.

“Our findings support a hypothesis that patients with USCD represent early celiac disease with a milder clinical phenotype presenting at a younger age with more infrequent nutritional deficiencies,” the researchers wrote, adding that “a single additional D1 biopsy specimen from any site increases the diagnostic yield [and] may reduce the known delay in diagnosis that many patients with celiac disease experience.”

“The lowly D1 has come of age,” Geoffrey Holmes, MD, Emeritus Consultant Gastroenterologist at The Royal Derby Hospital in the U.K., wrote in a related editorial. “Evidence indicates that a biopsy from D1 showing Marsh 3 changes may clinch the diagnosis of [celiac disease] when D2 shows lesser degrees of abnormality or is normal. Guidelines recommend taking biopsies from D1, but this has not yet been adopted widely in clinical practice. It should be, to maximize the change of diagnosing this eminently treatable condition.” – by Adam Leitenberger

Disclosure: The researchers report no relevant financial disclosures.