Noncoeliac enteropathy: the differential diagnosis of villous atrophy in contemporary clinical practice

BACKGROUND: Duodenal villous atrophy (DVA) is a key diagnostic finding in coeliac disease (CD). However, the differential diagnosis for this finding is broad. AIM: To identify conditions causing noncoeliac enteropathy (NCE) with villous atrophy and methods to differentiate between CD and NCE in clinical practice. METHODS: Through record review we identified patients with DVA due to conditions other than CD. Patient demographics, clinical features and relevant investigations were compared with CD patients. Rates of CD misdiagnosis, and response to treatments were recorded. RESULTS: Thirty cases of NCE were identified with ten different aetiologies. Unspecified immune-mediated enteropathy was the most common aetiology; affecting 10 patients. Gastrointestinal symptoms were more common in NCE than those in CD patients (P < 0.01). Twenty of the 24 NCE patients tested were HLA-DQ2/DQ8 negative. Twenty-six NCE patients were negative for IgA tissue transglutaminase (tTG) (P = 0.0001). Intraepithelial lymphocytosis was absent in 10 (33.3%) patients. Twenty-one NCE patients initially misdiagnosed with CD and one with gluten intolerance were prescribed a gluten free diet (GFD). Fifteen of 22 had repeat biopsy and none showed histological improvement. CONCLUSIONS: Although coeliac disease is the most common cause of DVA, noncoeliac enteropathy is not rare and may easily be mistaken for coeliac disease. Noncoeliac enteropathy is suggested by a normal initial tTG (87%), lack of intraepithelial lymphocytosis on biopsy, and lack of histological response to a gluten free diet. Subjective response to gluten free diet has poor predictive value for coeliac disease. Noncoeliac enteropathy can often be confirmed by negative HLA-DQ2/DQ8 testing and targeted investigations can ascertain a definitive aetiology in most cases.