Clinical and Immunologic Features of Ultra-Short Celiac Disease

Background & Aims The clinical effects of gluten-sensitive enteropathy with villous atrophy limited to the duodenal bulb (D1) have not been delineated in adults with celiac disease. We investigated the sensitivity of D1 biopsy analysis in the detection of celiac disease, the number and sites of biopsies required to detect ultra-short celiac disease (USCD, villous atrophy limited to D1), and the clinical phenotype of USCD. Methods We performed a prospective study of 1378 patients (mean age, 50.3 y; 62% female) who underwent endoscopy at a tertiary medical center in the United Kingdom from 2008 through 2014; routine duodenal biopsy specimens were collected from D1 and the second part of the duodenum (D2). Quadrantic D1 biopsy specimens were collected from 171 consecutive patients with a high suspicion of celiac disease (mean age, 46.5 y; 64% female). Clinical data from patients diagnosed with USCD, based on biopsy analysis, were compared with those from patients with conventional celiac disease (CCD) (villous atrophy beyond D1) and individuals without celiac disease (controls). The number of intraepithelial lymphocytes (IELs) and immune phenotypes were compared between D1 vs D2 in patients with celiac disease. Results Of the 1378 patients assessed, 268 (19.4%) were diagnosed with celiac disease; 9.7% of these patients had villous atrophy confined to D1 (USCD; P P P  = .03), had lower titers of tissue transglutaminase antibody ( P  = .001), and less frequently presented with diarrhea ( P  = .001) than patients with CCD. Higher proportions of patients with CCD had ferritin deficiency ( P  = .007) or folate deficiency ( P  = .003) than patients with USCD or controls. Patients with celiac disease had a median of 50 IELs/100 enterocytes in D1 and a median of 48 IELs/100 enterocytes ( P  = .7) in D2. The phenotype of IELs from patients with D1 celiac disease was indistinguishable from those of patients with D2 celiac disease. Conclusions Collection of a single additional biopsy specimen from any site in the D1 intestine increases the sensitivity of detection for celiac disease. Patients with USCD may have early stage or limited celiac disease, with a mild clinical phenotype and infrequent nutritional deficiencies.