Eosinophilic oesophagitis: clinical presentation and pathogenesis

Abstract

Eosinophilic oesophagitis (EoE) is an inflammatory disorder of the oesophagus which has become increasingly recognised over recent years, although it remains underdiagnosed in many centres. It is characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field), and clinically with features of oesophageal dysfunction such a dysphagia, food impaction, and proton pump inhibitor (PPI) resistant dyspepsia. Fibrosis and oesophageal remodelling may occur and lead to oesophageal strictures. An allergic predisposition is common in the EoE population, which appears to be primarily food antigen driven in children and aeroallergen driven in adults. Evidence suggests that the pathogenesis of EoE is due to a dysregulated immunological response to an environmental allergen, resulting in a T helper type 2 (Th2) inflammatory disease and remodelling of the oesophagus in genetically susceptible individuals. Allergen elimination and anti-inflammatory therapy with corticosteroids are currently the mainstay of treatment; however, an increasing number of studies are now focused on targeting different stages in the disease pathogenesis. A greater understanding of the underlying mechanisms resulting in EoE will allow us to improve the therapeutic options available.

Keywords: HISTOPATHOLOGY; IMMUNOLOGY; PUBLIC HEALTH.

Figure 1

Histology images of oesophageal epithelial eosinophilia. (A) Squamous mucosa showing basal cell hyperplasia, elongation of papillae, and numerous eosinophils in the epithelium (haematoxylin and eosin ×100). (B) Eosinophils in squamous epithelium (arrowhead, >30/high powered field). Detail upper right corner: eosinophilic micro abscess (arrow head, H&E ×400).

Figure 2

Mechanism of eosinophilic oesophagitis (EoE). Simplified diagram showing epithelial and immune cells in the oesophageal mucosa during EoE. The mucosa is subdivided into a stratified epithelial layer (Ep), lamina propria (LP) and the smooth muscle layer, mucosa muscularis (MM). Inflammatory cells infiltrating the epithelial layer are eosinophils (Eos, bilobar nuclei, red intracellular granules), and mast cells (MC with blue histamine containing granules). Eosinophils release granules (red stain). B cells (Bc), T cells (Tc) and dendritic cells (Dc) are present in the LP (the cells have been reported to be present in Ep and MM as well). T cells release IL-13 which induces eotaxin-3 production by epithelial cells. Eotaxin-3 is a specific chemoattractant for eosinophils attracting the cells from the peripheral blood. T helper type 2 (Th2) lymphocytes release IL-4 inducing an antibody isotype switch to IgE isotype in B cells. IgE binds to mucosal resident MC's facilitating granule release. Th2 lymphocyte derived IL-5 promotes survival of eosinophils. The epithelium produces thymic stromal lymphopoietin (TSLP) and stimulates Dc's to present allergens for Th2 Lymphocytes. Whitish exudates are present at the epithelium surface due to accumulation of eosinophils. Medications such as proton pump inhibitors (PPIs) may act in an anti-inflammatory capacity through inhibition of the allergy associated transcription factor signal transducer of activator of transcription 6 (STAT-6) or by altering epithelial permeability. Medications such as antibiotics may additionally promote EoE by skewing the immune response from a Th1 to Th2 type. Transforming growth factor β (TGF-β) released by epithelial cells, MC, and Eos induces activation of fibroblasts augmenting fibrosis in the LP and contraction of the mucosa muscularis (MM), the combination of which may lead to pathological features such as strictures.