The use of small-bowel capsule endoscopy in cases of equivocal celiac disease

Abstract: Background and aims Seronegative villous atrophy (SNVA), raised intraepithelial lymphocytes (IELs) and crypt hyperplasia on duodenal histology can be secondary to celiac disease (CD) or other causes such as medications or infections. Our aims were to assess the role of small-bowel capsule endoscopy (SBCE) in these patients and to ascertain whether findings on SBCE at diagnosis can predict disease outcome. Methods Patients (177) with SNVA, IELs +/-crypt hyperplasia on duodenal histology were studied. These patients all had an equivocal diagnosis of CD. Results Overall, 56 (31.6%) patients had a positive SBCE. Most patients had disease affecting the proximal third of the small bowel (SB) (33, 58.9%). The diagnostic yield of SBCE was 40.0% (22 patients), 51.4% (18 patients), 27.0% (10 patients), and 14.0% (7 patients) in patients with an unknown cause for SNVA (SNVA-UO), patients with SNVA who responded to a gluten-free diet (SNVA-CD), SNVA-KNOWN CAUSE, patients with railed intraepithelial lymphocytes +/- crypt hyperplasia respectively. In SNVA-UO, SBCE at diagnosis was more likely to be positive in patients with persistent SNVA (10, 90.9%) and persistent SNVA with lymphoproliferative features (4, 80.4%) than patients with spontaneous resolution of SNVA (8, 20.5%) (p=0.0001). All patients in the SNVA-CD group who eventually developed adverse events had a positive SBCE (p=0.022). They also had more extensive SB disease than those without adverse events (50% vs 1% p=0.002). More-extensive SB disease on SBCE correlated with a higher SNVA-related mortality in patients with SNVA-UO and SNVA-CD (p=0.019). Severity of histology did not correlate with mortality (p=0.793). Conclusions A positive SBCE at diagnosis predicts a worse outcome. More importantly, more extensive disease in these patients is associated with poor survival. Targeting patients with extensive disease at diagnosis with more aggressive therapy can help to improve prognosis.