ObjectiveVillous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies.Patients and methodsClinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed.ResultsBetween September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients.ConclusionPatients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.