Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios

Abstract

Introduction. Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard. Aim. We wanted to test the uniformity of application of Marsh–Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis. Methods. We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten-containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh–Oberhuber classification. Cohen κ inter-test was used for evaluating the agreement between histologists regarding group A. Results. Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results. Discussion. Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh–Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure.

Key Words::

• celiac disease
• histology
• in vitro
• organ culture
• serology

Acknowledgment

The manuscript, as submitted, has been reviewed by and approved by all named authors; all authors made a substantive contribution to the study; the corresponding author is empowered by all of the authors to act on their behalf with respect to the submission of the manuscript; the article is original.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. The article does not infringe upon any copyright or other proprietary right of any third party; the text or the data reported have not been published previously; the article or a substantially similar article is not under consideration by another journal at this time. There are not financial or other relationships that might lead to a conflict of interest.