Gluten sensitivity and 'normal' histology: is the intestinal mucosa really normal?

BACKGROUND: Early pathogenetic events of gluten intolerance may be overlooked in patients with serologic markers of celiac disease and normal intestinal mucosa by both conventional histology and immunohistochemistry. AIMS: To investigate if a submicroscopical damage of the absorptive cell surface was associated with developing gluten sensitivity. PATIENTS AND METHODS: Duodenal biopsies of seven subjects with positive anti-endomysial antibodies and normal histology underwent ultrastructural evaluation of the epithelial surface by means of both scanning and transmission electron microscopy. Specimens of intestinal mucosa of 14 children with non-celiac conditions were used as controls. RESULTS: In four patients, electron microscopy revealed alterations of the enterocyte brush border with a significant reduction of the height of microvilli. After several months, three of them had a second biopsy that eventually showed histological modifications suggestive of celiac disease. In the other three patients, no significant alteration of enterocyte ultrastructure was observed. One of them, rebiopsied after 12 months, still showed a normal duodenal histology. CONCLUSIONS: Gluten sensitivity can be associated with 'minimal' mucosal changes not detectable with conventional light microscopy. Such lesions, which primarily involve microvillous structure, may imply a reduction of intestinal absorptive surface already in the latent stage of the disease.