VANCOUVER, B.C.—Eosinophil-derived neurotoxin is a practical, simple and useful biomarker for eosinophilic esophagitis, according to a new study comparing EDN with other diagnostic tools.
“We are already using EDN testing at our center. It can clarify the diagnosis in challenging cases, it is easy to use, and it is not expensive,” reported Yamen Smadi, MD, a pediatric gastroenterologist at the Arnold Palmer Hospital for Children, in Orlando, Fla.
There are many challenges in the diagnosis of EoE, Dr. Smadi noted. They include patchy distribution of eosinophils increasing miss rates for biopsies and high rates of eosinophil degradation, leading to problems with hematoxylin and eosin staining. When biopsies do not provide a definitive diagnosis, it can lead to delayed or inappropriate care.
In this study, which won a Presidential Poster Award at the 2023 annual meeting of the American College of Gastroenterology (abstract P1857), Dr. Smadi and his co-investigators evaluated levels of EDN in 231 children seen at Arnold Palmer Hospital between 2014 and 2018. Of these patients, 140 had a history of EoE and 140 served as controls. About half of the sample was white, with the remaining patients identifying as Hispanic, Black or Asian. The mean age was 10.3 years. The investigators obtained EDN via esophageal brushing and analyzed it in relation to the endoscopic reference score (EREFS) and peak eosinophil count (PEC).
EDN Correlates With EoE Scores
Based on a previous study establishing EDN as a biomarker for EoE, elevated EDN was defined as a value higher than 10 mcg/nL (Dis Esophagus 2018;31[12]:12). Active EoE was defined as PEC of at least 15 cells per high-power field.
Dr. Smadi reported that levels of EDN strongly correlated with both EREFS and PEC levels on the basis of Spearman’s rho analysis (P<0.0001). Overall, the EDN levels had an 84.4% sensitivity for EoE activity and a 94.6% specificity.
When distribution of eosinophilia was stratified, EDN levels were higher for children with eosinophilia at more than one level than for those with eosinophilia exclusive to the distal, middle or proximal areas of the esophagus, Dr. Smadi reported. In cases where eosinophilia was found only in the distal esophagus, positive EDN concentrations were significantly related to higher EREFS scores (P<0.001) but not PEC scores.
Dr. Smadi said EDN concentrations were higher in children with positive PEC and positive EFEFS than in those with positive PEC and negative EREFS.
EDN Can Be an Adjunctive Diagnostic Tool
Dr. Smadi asserted that his data and experience support this as a tool that can be applied now in daily practice. “The brushing can be readily performed with routine endoscopy, and the information can be helpful in selected patients,” he said.
“EDN measured in esophageal brushing samples during endoscopy is an objective and accurate reflection of EoE disease activity,” he said. “It provides a valuable adjunctive tool in the diagnosis of EoE, especially when esophageal distribution is unequal and when endoscopy and histology results do not correlate.”
An investigator in Korea, Yunju Jo, MD, PhD, of the Division of Gastroenterology at the Eulji School of Medicine, in Seoul, drew the same conclusion 10 years ago. In a small study that evaluated EDN as a biomarker for EoE, all EoE patients had positive staining for EDN versus none of the histologically normal controls (J Neurogastroenterol Motil 2010;16[4]:446-447).
As a result, Dr. Jo concluded that the evaluation of EDN in esophageal biopsy specimens from patients suspected of having EoE appears to be “a useful means to diagnose and manage” these patients.
Asked to comment, Stuart J. Spechler, MD, the chief of the Department of Gastroenterology and Hepatology at Baylor University Medical Center, in Dallas, told Gastroenterology & Endoscopy News that there is a need for a biomarker given the potential for missed eosinophilia on esophageal biopsies. However, he considers that need to be “limited.”
While he is not convinced yet of the value of EDN as a practical and reliable diagnostic tool, he foresaw possible applications if larger studies confirm its utility.
“My group has hypothesized that there is a muscle-predominant form of EoE that might be responsible for some cases of achalasia and other motility disorders,” he said. Given the difficulty of obtaining biopsies of esophageal muscle, Dr. Spechler speculated that a biomarker like EDN might address this issue. Studies investigating this question are needed.
—Ted Bosworth
Drs. Jo and Smadi reported no relevant financial disclosures. Dr. Spechler reported financial relationships with Castle Biosciences, Interpace, Ironwood, ISOThrive, Phathom and Takeda.
This article is from the February 2024 print issue.