AIMS--To highlight the pitfalls in the diagnosis of coeliac disease and to make recommendations for its diagnosis and the management of refractory cases with equivocal histology. METHODS--Six patients, referred since 1989 with a diagnosis of coeliac disease based on duodenal biopsy specimens taken at endoscopy, and who failed to respond to a gluten-free diet were studied. All patients were subjected to peroral jejunal biopsy. Morphometric analysis of villus height:crypt depth ratios, surface enterocyte cell heights, and intraepithelial counts was used to aid in the assessment of equivocal histology. RESULTS--Subsequent small intestinal biopsy specimens both taken when the patients were following a gluten-free diet and after gluten challenge were normal in all cases. Morphometric analysis and intraepithelial counts were normal. CONCLUSIONS--Misinterpretation of the original slides was often due to poor sample quality and tangential sectioning. Failure to respond to a gluten-free diet should always raise doubt regarding the initial diagnosis, especially when the findings are normal. For correct diagnosis at least three distal duodenal biopsy specimens should be taken simultaneously, and these should be of an adequate size and correctly orientated. Review by a histopathologist experienced in gastrointestinal diagnosis is essential in difficult cases. Quantitative morphometric analysis is helpful in equivocal cases, and jejunal suction biopsy, following a gluten challenge, may be necessary in patients refractory to treatment.
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