Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Dec 5, 2018; 9(6): 55-62
Published online Dec 5, 2018. doi: 10.4292/wjgpt.v9.i6.55
Coeliac disease in the modern era: Severity of small bowel mucosal injury at diagnosis with analysis of clinical correlates and rate of improvement on a gluten free diet
Oliver Cronin, Emma Flanagan, Damian Dowling
Oliver Cronin, Damian Dowling, Department of Gastroenterology, University Hospital Geelong, Geelong 3220, Australia
Emma Flanagan, Department of Gastroenterology, St Vincent’s Hospital, Fitzroy 3065, Australia
Author contributions: Dowling D designed the research and critically revised the manuscript; Flanagan E collected the data; Cronin O analyzed the data and wrote the manuscript.
Institutional review board statement: This study was reviewed and approved by the Barwon Health Human Research Ethics Committee (Geelong, Australia).
Conflict-of-interest statement: There are no conflicts of interest to report.
STROBE statement: Guidelines from the STROBE statement have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Oliver Cronin, MBBS, Doctor, Department of Gastroenterology, University Hospital Geelong, Ryrie St & Bellerine St, Geelong 3220, Australia. oliver.cronin@barwonhealth.org.au
Telephone: +61-3-42150000 Fax: +61-3-42150000
Received: May 25, 2018
Peer-review started: May 25, 2018
First decision: June 13, 2018
Revised: July 9, 2018
Accepted: July 21, 2018
Article in press: July 21, 2018
Published online: December 5, 2018
Processing time: 194 Days and 16.6 Hours
ARTICLE HIGHLIGHTS
Research background

Coeliac disease (CD) is a common gastrointestinal disorder that involves an immune response to dietary gluten. The condition is under recognised, particularly because silent or atypical presentations are becoming more common. Diagnosis is made with the combination of symptoms, serology and characteristic features seen on duodenal biopsy. It remains unclear whether there is an association between symptoms at diagnosis and the degree of small bowel injury. In addition, it is unclear whether symptoms and serology at the time of repeat duodenal biopsy are associated with the degree of mucosal healing.

Research objectives

The aim of this study was to analyze the association between both pre-diagnosis coeliac serology and initial duodenal histopathology, and primary presenting symptoms, coeliac related comorbidity and response to a gluten-free diet (GFD). Most patients in this study were asymptomatic at diagnosis. Neither symptoms nor serology were associated with the severity of small bowel injury. Many patients had persistent mucosal damage at the time of repeat duodenal biopsy despite reported adherence to a GFD suggesting that mucosal healing may take longer than previously reported. These findings have revealed the increasing difficulty in recognizing the symptoms of CD. Further research is needed to develop more reliable non-invasive biomarkers to be used as surrogates to assess mucosal healing.

Research methods

This was a retrospective cohort study which included 99 participants who presented to a single Gastroenterology practice in Victoria, Australia from 1999-2013. Patients were referred from General Practitioners or other specialists. All patients were assessed by a Gastroenterologist. Data recorded included: baseline demographics, co-morbidities, family history, duration of symptoms, complications of CD. Serology and histology results were recorded for each patient. The majority of these patients underwent repeat duodenal biopsy after a period on a GFD to check for mucosal healing. Results were compared to repeat serology and symptoms. Numerical data were presented as median and inter-quartile range (IQR). The association of severity of duodenal blunting to symptoms and serology were examined using logistic regression.

Research results

The mean age at diagnosis was 43 years (IQR 30-53 years) and the majority was female. Most patients (n = 51, 52%) were asymptomatic at diagnosis. 17 (17%) patients had an associated autoimmune condition, the majority of whom had thyroid pathology (n = 10, 59%). The majority of patients with Marsh-Oberhuber Score (MS) ≥ 3a were symptomatic at diagnosis. There was no difference in symptoms between patients in a combined group of MS 3a/b compared to MS 3c. There was no difference of concomitant autoimmune conditions between patients with MS 3a/b (n = 4, 10%) and MS 3c (n = 9, 18%). Multivariate analysis did not reveal an association between MS ≥ 3a at diagnosis of CD and positive serology or symptoms at diagnosis. 87 (88%) patients had repeat biopsy. Lack of improvement in small bowel histology was not associated with persistently positive coeliac serology or ongoing symptoms at the time of repeat biopsy.

Research conclusions

This study supports larger studies that have reported an increase in asymptomatic presentations of CD. Severity of villous blunting at diagnosis was not associated with symptoms. This study did not find an association between symptoms and serology at the time of repeat duodenal biopsy with persistent villous blunting. Duodenal healing whilst on a GFD may persist for longer than previously reported. Discovery of new non-invasive biomarkers is needed to better predict the degree of villous blunting.

Research perspectives

Duodenal healing whilst on a GFD may persist for longer than previously reported. Discovery of new non-invasive biomarkers is needed to better predict the degree of villous blunting.