A Comprehensive Assesment of Eosinophilic Oesophagitis

Abstract

Introduction Eosinophilic oesophagitis (EoE) is an uncommon disease that has recently been experiencing an increase in incidence and prevalence. Due to the similarities, it is challenging to distinguish EoE from its primary differential diagnosis, gastro-oesophageal reflux disease (GORD). The lack of a diagnostic adjunct further compounds this issue, although immunoglobulin G4 (IgG4) staining has recently shown some potential. The onset of disease has been established in both children and adults, but there is limited understanding regarding the natural history of this condition. Furthermore, an incomplete comprehension of EoE pathogenesis has led to uncertainty regarding the correlation between its clinical and endoscopic variables. Aims This thesis aimed to: 1. Evaluate the role of oesophageal mucosal IgG4 staining as a diagnostic adjunct for EoE. 2. Investigate the natural history of childhood-onset and adult-onset EoE. 3. Characterise and differentiate the oesophageal endoscopic appearance, wall thickness, histology, and motility in adults with EoE and GORD. 4. Identify markers of disease progression in EoE. Methods A literature review was performed, highlighting the differences and potential relationship between EoE and GORD. Subsequently, a retrospective analysis was completed examining the role of oesophageal mucosal IgG4 staining in differentiating EoE from GORD. Next, a crosssectional, questionnaire-based study compared the characteristics and disease progression between childhood-onset and adult-onset EoE. Following this, a prospective, interventional study characterising and comparing the anatomy, histology, and motor function in EoE and GORD subjects was accomplished. Finally, a longitudinal study was carried out to assess the potential changes in the oesophageal wall of EoE subjects. Results The prevalence of positive IgG4 stain was higher in the EoE compared to GORD with high sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Most of those with childhood-onset and adult-onset EoE were found to have a long duration of symptoms before and after the diagnosis despite treatment. Childhood-onset EoE was progressive from childhood to adulthood but was associated with more inflammatory-type symptoms post transition. Although total oesophageal wall thickness was comparable between EoE and GORD, the thickness of the submucosa in the distal oesophagus was higher in EoE. Positive correlations were found between dysphagia score and distal total oesophageal wall thickness, as well as disease duration and distal submucosal thickness only in EoE. Lastly, distal total oesophageal wall thickness increased over time in EoE independent of dysphagia score and eosinophil count. Conclusions IgG4 staining in oesophageal biopsies was a valuable marker for distinguishing EoE from GORD. EoE appears to be a progressive, chronic disease, the onset of which may occur in childhood or adulthood. Inflammatory-type symptoms persisted in those with childhood-onset EoE. Distal oesophageal wall thickness correlates positively with dysphagia score in EoE but not GORD due to the composition of the submucosa, which is identifiable via endoscopic ultrasound (EUS). Distal total oesophageal wall thickness increased with time in EoE, but this was not associated with a change in dysphagia or eosinophil count.