Quantitative Analysis of Tug Sign: An Endoscopic Finding of Eosinophilic Esophagitis

Background: Eosinophilic esophagitis (EoE) is a relatively common, immune-mediated cause of esophageal inflammation and dysfunction. Clinical symptoms of EoE, such as dysphagia and food impactions, are likely secondary to fibrostenotic tissue remodeling. Endoscopists have long appreciated a firmness of the esophageal mucosa when obtaining EoE biopsies. This “tug” or “pull” sign is felt to correlate with disease activity, likely due to degree of tissue fibrosis. Quantitative measurements of these signs have not been determined. Our aim was to measure the quantifiable difference in the Newton forces required to obtain esophageal biopsies in patients with and without EoE.

Methods: Patients undergoing esophagogastroduodenoscopy (EGD) for history of or suspected EoE were approached for enrollment. Exclusion criteria were known history of IBD, connective tissue disorders, or tracheoesophageal fistula. To measure force, a screw compressor clamp was attached at the most distal positioning marker of a 2.8 mm radial jaw forceps (Boston Scientific). The clamp provided a stable position to attach a Newton force gauge (Nidec-Shimpo FG-3006) (Image 1). Maximum forces required to obtain up to 6 esophageal biopsies per patient were measured, from which mean force and peak force per patient were calculated. Total eosinophil counts per high power field (eos/hpf), presence of tissue fibrosis, and Eosinophilic Esophagitis Endoscopic Reference Score (EREFS) were obtained. Clinical assessments were measured with Pediatric Eosinophilic Esophagitis Symptom Severity module (PEESSv2.0).

Results: 131 pediatric patients age 1-21 years were enrolled (70 EoE; 61 controls). In total, we biopsied 417 specimens from EoE patients and 364 specimens from controls (Table 1). Patients with EoE showed a significant increase in both mean force (16.4N +/- 6.8 vs 12.4N +/- 3.6, p<0.001) and peak force (22.2N +/- 7.7 vs 15.9N +/- 4.4, p<0.001, Fig 1). The optimal peak force that would label a patient as EoE was 19N (Sen 0.66, Spec 0.85, AUC 0.75) by Youden index. Biopsy size did not affect the biopsy force. Positive correlation was observed between peak force and increased fibrosis on biopsy, EREFS, the dysphagia questions of the PEESS, and the subject’s age (Spearman R=0.42, 0.38, 0.43, and 0.29, p≤0.01). No correlation was observed between overall PEESS score or specific number of eos/hpf with peak force.

Conclusion: We describe a new technique of esophageal biopsy which allows the measure of Newton force required to obtain a tissue sample in patients with EoE. We show for the first time that obtaining biopsies in patients with EoE requires significantly more force relative to non-EoE controls. Measuring a peak force appears to be both sensitive and specific for the identification of EoE, and increased force for biopsy correlates with tissue fibrosis and dysphagia. Ultimately, the measurement of tensile force may serve as an additional tool in the diagnosis, prognosis and management of EoE.