Endoscopy in eosinophilic esophagitis: within or beyond the reach of the endoscope?

Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus. In order to establish the diagnosis of EoE, the following criteria should be met: presence of symptoms of esophageal dysfunction and predominantly eosinophilic inflammation of the esophagus [1]. Unlike the clinical manifestations and histologic findings, the diagnostic yield of endoscopy has been regarded as limited, because initially visible mucosal alterations were reported as being either unremarkable or even absent [2] [3]. However, in recent years it has become evident that the majority of patients with EoE present with a number of mucosal alterations that are clearly visible on endoscopy [4]. Subsequently, a grading and classification system assessing the five major EoE-associated endoscopic signs (edema, rings, exudates, furrows, strictures, [EREFS]) was developed [5]. Three of these signs – edema, white exudates, and furrows – were attributed to inflammatory changes, whereas the remaining two – rings and strictures – were thought to represent the features of remodeling.

The eosinophil is a late-phase inflammatory cell that plays an important role in tissue repair and remodeling [6]. There is solid evidence to show that unbridled eosinophilic inflammation induces fibrosis with luminal narrowing and stricture formation, finally resulting in an alteration of esophageal function [7] [8]. There is also good evidence to indicate that EoE is a progressive fibrostenotic disease as the extent of fibrosis has been positively associated with disease duration [9] [10]. As such, at the beginning of the disease, physicians are likely to find patients with only inflammatory features. However, as disease progresses, a mixture of the inflammatory and fibrotic features is observed. Based on the findings of several clinical trials we know that both the inflammatory as well as the remodeling component can cause dysphagia [11] [12]. However, remodeling is likely to be the main risk factor for longstanding food-impaction [13].

The assessment of the extent of remodeling is a challenge. Endoscopy is not able to determine reliably the size of the esophageal lumen, and wall thickening can only be measured by endoluminal sonography. Imaging techniques, such as barium swallow or computed tomography (CT), and established functional examinations are not reliable in assessing the degree of remodeling [4]. In summary, determining the extent of esophageal fibrosis remains a challenge. The newly developed high-resolution impedance planimetry with functional lumen imaging probe (FLIP) is a promising technique to determine the functional properties of the esophagus and the stage of remodeling [14].

In this issue of Endoscopy, Chen and co-workers present a study evaluating the associations between the endoscopic alterations seen in EoE and the results of distensibility measurements [15]. The authors assessed endoscopic alterations, esophageal distensibility, and the extent of eosinophilic tissue infiltration in 72 adult EoE patients. Endoscopic features of edema, rings, exudates, furrows, and stricture were evaluated using the EREFS grading and classification system; distensibility metrics were obtained using the FLIP; and density of eosinophils was measured in hematoxylin and eosin (H&E)-stained tissue sections. The authors found a significant association between the severity of exudates and furrows and the eosinophil density in the tissue. In addition, increased ring severity was associated with reduced distensibility. In contrast, the severity of exudates and furrows and the degree of eosinophilia showed no association with the distensibility parameters.

This study confirms that endoscopy is a useful tool in the diagnosis of EoE. Furthermore, endoscopy is able not only to detect EoE, but in addition to estimate the degree of inflammation and the extent of remodeling. The use of the EREFS classification allows the physician to identify patients with inflammatory and/or fibrotic features. The findings of the study have several practical consequences.

First, endoscopists should be aware that, in the majority of patients, EoE can be recognized endoscopically based on several typical findings. Endoscopy has a much higher diagnostic yield than originally thought and does not serve only as a tool to obtain biopsies.

Second, this study indicates that a systematic assessment of the five EoE-associated features (edema, rings, furrows, exudates, and strictures) allows a physician to classify a patient within the inflammation/fibrosis spectrum and potentially to estimate his/her risk of experiencing a food impaction. An endoscopist’s overall impression of the EoE activity without the systematic assessment of these features is no longer appropriate when examining EoE patients.

Third, because patients with predominant inflammation might respond differently to a particular drug from patients with predominantly fibrotic features, patients participating in clinical trials should be stratified into these groups and examined separately.

Lastly, this study raises the question of whether endoscopy should, in addition to symptoms and histology, be included in the list of diagnostic criteria for EoE.

However, this study has one important limitation – it was performed by expert endoscopists with a particular knack for identifying the various features of EoE. Additional studies will show us whether these findings can be confirmed and provide evidence as to the utility of the EREFS grading and classification system in daily clinical usage.

• References

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