Non-oesophageal Eosinophilic Gastrointestinal Diseases Are Undersuspected Clinically and Underdiagnosed Pathologically

Robert M. Genta; Evan S. Dellon; Kevin O. Turner


Aliment Pharmacol Ther. 2022;56(2):240-250. 

In This Article

Abstract and Introduction


Background: Non-oesophageal gastrointestinal eosinophilic diseases (EGID) are considered rare. However, low disease awareness among clinicians and pathologists may contribute to underdiagnosis.

Aims: To determine how frequently requests to evaluate for EGID accompany gastrointestinal biopsies and in what proportion of suspected cases pathologists address these requests, either confirming or refuting the clinical suspicion.

Methods: All cases in which biopsy requisitions included an explicit suspicion of EGID were extracted from a large clinicopathologic database and manually reviewed for accuracy. The diagnoses for these cases were then analysed to determine whether clinical suspicions were confirmed, refuted or ignored.

Results: Eosinophilic oesophagitis (EoE) was suspected in 12.8% of 903,516 patients with biopsies and confirmed in 14.9% of them. A suspicion of eosinophilic gastritis accompanied <0.001% of 1,438,206 gastric biopsy sets and was confirmed in 11.5% of them; eosinophilic duodenitis was suspected in 0.02% of ~675,519 patients with duodenal biopsies and confirmed in 8.0% of these; eosinophilic colitis was mentioned in <0.001% of 2,504,485 patients with colonic biopsies and confirmed in 0.1% of them. Less than 3% of endoscopists mentioned non-oesophageal EGID in the requisition, while most expressed a clinical suspicion of Barrett oesophagus, Helicobacter pylori gastritis, celiac disease and microscopic colitis (in 21.2%, 49.2%, 1% and 6.4% of the cases, respectively).

Conclusions: Gastroenterologists and pathologists commonly address and diagnose EoE. In contrast, both clinical suspicion and diagnosis of non-oesophageal EGID are extremely rare. Increased clinical awareness might result in a better understanding of the epidemiology and improved diagnosis of these still elusive conditions.


Eosinophilic gastrointestinal diseases (EGIDs) are chronic inflammatory conditions characterised by persistent gastrointestinal (GI) symptoms and pathologically elevated levels of activated eosinophils in the GI tract.[1] The manifestations of eosinophilic esophagitis (EoE) have been characterised[2] and guidelines for the clinical and histopathologic components of the diagnosis are accepted by most clinicians and pathologists.[3,4] In contrast, non-oesophageal EGID, which include eosinophilic gastritis, duodenitis and colitis (EoG, EoD and EoC),[5] present with nonspecific symptoms (early satiety, nausea and vomiting, abdominal pain and cramping, bloating, and diarrhoea) that overlap with other common GI conditions, such as functional dyspepsia, irritable bowel syndrome or inflammatory bowel disease. Significant endoscopic findings are frequently absent and, when present, are non-specific.[6] As a result, clinicians may not suspect EGIDs and many patients face a long delay with suboptimal care before the correct diagnosis is made.[7]

The final diagnosis of EGID hinges on a histopathologic report of biopsies with significantly elevated mucosal eosinophilic infiltrates. However, pathologists' awareness of EGIDs is reportedly low, requests to consider EGID in the requisitions that accompany GI biopsies are believed to be rare, there are no accepted thresholds for normal eosinophilic counts in the gastrointestinal tissues (which makes counting eosinophils an unpopular exercise), and there are no guidelines on which to base the diagnosis.[8–10] While most pathologists are now aware of EoE, evaluate the numbers of eosinophils in squamous oesophageal biopsy specimens and, when their density is elevated, report the peak number of eosinophils in a high-power field (hpf), a diagnosis of EGID remains a curiosity.

While a low awareness of EGID by both clinicians and pathologists is often invoked to explain the rarity of these diagnoses,[11] it has never been studied systematically or quantified. This study was designed with two primary goals: to determine how frequently a request to evaluate for EGID accompanies a GI biopsy specimen, and in what proportion of suspected cases the pathologist addresses the request in the histopathologic report, either by confirming or refuting the clinical suspicion.