AIM: To assess the evolution of duodenal lymphocytosis(DL), a condition characterized by increased intraepithelial lymphocytes(IELs), over 2 years of follow-up.METHODS: Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease(CD) were included. Evaluation of IELs infiltrate in duodenal biopsy sampleswas carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: Ig G and Ig A anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance i m a g i n g w e r e p e r f o r m e d w h e n n e c e s s a r y. R i s k factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR.RESULTS: Eighty-five patients(16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15-25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed Ig G anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity(GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn’s disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack of diagnostic evidence. At multivariate analysis, the evolution towards CD was associated with an IELs infiltrate > 25(OR = 1640.4) or 15-25(OR = 16.95), human leukocyte antigen(HLA) DQ2/8(OR = 140.85) or DQA1*0501(OR = 15.36), diarrhea(OR = 5.56) and weakness(OR = 11.57). GS was associated with IELs 15-25(OR = 28.59), autoimmune thyroiditis(OR = 87.63), folate deficiency(OR = 48.53) and diarrhea(OR = 54.87).CONCLUSION: DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS. AIM: To assess the evolution of duodenal lymphocytosis (DL), a condition characterized by increased intraepithelial lymphocytes (IELs), over 2 years of follow-up. METHODS: Consecutive patients undergoing upper endoscopy / histology for abdominal pain, diarrhea, weight loss, Weakness or other extraintestinal features compatible with celiac disease (CD) were included. Evaluation of IELs infiltrate in duodenal biopsy sampleswas carried out by CD3-immunohistochemistry and expressed as number of positive cells / 100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: Ig G and Ig A anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and / or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgr Rthk factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR.RESULTS: Eighty-five patients (16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 months. At baseline, endoscopy / duodenal biopsy, CD3 immunohistochemistry revealed:> 25 IELs / 100 enterocytes in 22 subjects, 15-25 IELs in 37 and <15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed Ig G anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity (GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn’s disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndr omAt multivariate analysis, the evolution toward CD was associated with an IELs infiltrate> 25 (OR = 1640.4) or 15-25 (OR = 16.95), human leukocyte antigen (HLA) DQ2 / 8 OR = 140.85) or DQA1 * 0501 (OR = 15.36), diarrhea (OR = 5.56) and weakness folate deficiency (OR = 48.53) and diarrhea (OR = 54.87). CONCLUSION: DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS.