Lymphocytic Duodenosis and the Spectrum of Celiac Disease

OBJECTIVES: Celiac disease (CD) is a chronic inflammatory disease of the small bowel that is characterized by increased intraepithelial lymphocytes (IELs) and villous atrophy of the mucosa. It is unclear how often intraepithelial lymphocytosis in the absence of atrophy is a manifestation of gluten sensitive enteropathy. The objective of this study was to identify factors that discriminate patients with CD from those with lymphocytic duodenosis (LD, intraepithelial lymphocytosis without villous atrophy). We compared Class 2 HLA type, presenting symptoms, and serology in patients with LD and CD. METHODS: Retrospective review of 124 systematically assessed patients with LD compared with 454 CD patients with villous atrophy. All patients had duodenal biopsies and Class 2 HLA typing performed. HLA type, symptoms, serology pattern, and response to a gluten-free diet were analyzed using univariate logistic regression modeling, adjusted for age and gender. RESULTS: Half of the (63 (51 %)) LD patients lack the Class 2 HLA genotypes encoding DQ2 or DQ8 whereas only 11 (2 %) CD patients had neither DQ2 nor DQ8, P < 0.001. The genes encoding DQ2 were much more prevalent in CD (91 %) than that in LD (37 %, P < 0.001), however, the rate of carriage of DQ8 did not differ between the two groups (15 % vs. 15 %, P = 0.9). Although diarrhea and weight loss were equally frequent in LD and CD patients, LD patients were less likely to be associated with anemia (P = 0.007), malaise (P = 0.006), skin disorder (P = 0.007), or a family history of CD (P < 0.001). The LD subjects were much less likely to have tissue transglutaminase or endomysial antibodies than were CD subjects (12 % or 0 % vs. 87 % and 87 %; P < 0.001, respectively). CONCLUSIONS: The LD cohort differs significantly in terms of HLA type, serology, and clinical features, suggesting that the majority of patients with LD do not belong in the spectrum of CD.