Non-Invasive and Minimally Invasive Biomarkers for the Management of Eosinophilic Esophagitis beyond Peak Eosinophil Counts: Filling the Gap in Clinical Practice

Abstract

Eosinophilic esophagitis (EoE) is a chronic esophageal disease that needs lifelong management and follow-up. The diagnosis requires an upper endoscopy with at least one esophageal biopsy demonstrating >15 eosinophils/high-power field, and often occurs with a diagnostic delay of up to ten years, partly due to the absence of valid non-invasive screening tools. In addition, serial upper endoscopies with esophageal biopsies are mandatory to assess the efficacy of any ongoing treatment in patients with EoE. These procedures are invasive, costly, and, when performed without sedation, are often poorly tolerated by patients. Therefore, there is the clinical need to identify reliable non-invasive or minimally invasive biomarkers that could be used to assess disease activity in clinical practice as a surrogate of peak eosinophil counts on esophageal biopsies. This review summarizes evidence on investigational non-invasive or minimally invasive biomarkers for the diagnosis and follow-up of EoE to report on the state of the art in the field and support future research. We discussed eosinophil-derived mediators including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN, also known as eosinophil protein X), eosinophil peroxidase (EPO), and major basic protein (MBP) as well as other promising non-eosinophil-derived biomarkers. Although several studies have shown the utility of most biomarkers collected from the serum, esophageal luminal secretions, and feces of EoE patients, numerous limitations currently hamper the integration of such biomarkers in clinical practice. Future studies should aim at validating the utility of non-invasive and minimally invasive biomarkers using rigorous protocols and updated consensus criteria for EoE.

Review of Non-Eosinophilic Esophagitis-Eosinophilic Gastrointestinal Disease (Non-EoE-EGID) and a Case Series of Twenty-Eight Affected Patients

“…Serum anti-Helicobacter pylori antibody positivity has been found to be lower in cases with non-EoE-EGID than in a control group [ 20 ]. Unfortunately, no specific sensitive blood biomarker has been reported for diagnosing adult cases with non-EoE-EGID or severity assessment, although some non-invasive and minimally invasive biomarkers for EoE are under investigation [ 21 , 22 , 23 , 24 ]. Fecal calprotectin has been reported to be increased in cases with EGID and may be a screening marker for EGID [ 24 ].…”

“…Fecal calprotectin has been reported to be increased in cases with EGID and may be a screening marker for EGID [ 24 ]. Increased fecal eosinophil granular proteins, such as eosinophil cationic protein, may be diagnostic markers indicating EGID, although more results are needed to confirm their usefulness [ 23 , 25 ].…”