What's GERD Got to Do with DES: Comparing Characteristics of Reflux and Non-Reflux Phenotypes of Distal Esophageal Spasm

Introduction: Distal esophageal spasm (DES) is a rare motility disorder characterized by ≥20% premature contractions (distal latency ≤ 4.5s) and a distal contractile integral of ≥450 mmHg·s·cm on high-resolution manometry (HRM). Cardinal symptoms of DES include dysphagia and non-cardiac chest pain. Previous studies suggested a potential association between DES and gastroesophageal reflux disease (GERD) based on endoscopic findings or acid perfusion. However, the recommendation for DES management is to “optimize GERD treatment,” despite limited supporting data. This study aims to investigate symptomatic and manometric differences among DES patients with and without GERD on quantitative testing. Methods: A retrospective cohort study was conducted using HRM and reflux testing from 2/2020-12/2022. Exclusion criteria included type III achalasia or prior foregut surgery. Participants with DES on HRM were characterized by reflux testing results. The reflux DES group (R-DES) included individuals with endoscopic evidence of GERD (Los Angeles grade C/D esophagitis or Barrett’s) or elevated acid exposure on 24–48-hour pH testing. The non-reflux group (NR-DES) consisted of patients with normal 24–48-hour reflux testing. Descriptive and univariate analyses were performed comparing R-DES to NR-DES subjects. Results: A total of 99 eligible subjects with DES were identified, with 66 undergoing reflux testing and 2 with Barrett’s. The R-DES cohort included 32 subjects and NR-DES cohort had 36 subjects. Compared to NR-DES, R-DES subjects weighed more (mean BMI 30.33, 26.93, P = 0.012). Both groups exhibited similar usage rates of proton pump inhibitors (78.1%, 91.7%, P=0.218) and chronic opioids (10%, 5.6%, P=0.652). No significant differences between groups were observed with respect to presenting symptoms (heartburn, regurgitation, abdominal pain, globus sensation, belching, nausea/vomiting, dysphagia, or chest pain) or HRM metrics (hiatal hernia size, basal LES pressure, residual LES pressure, or bolus clearance) (Table 1). Conclusion: Despite the long-believed association between DES and GERD, this study demonstrates that DES patients with and without GERD do not exhibit phenotypic differences in symptom presentation or HRM metrics associated with GERD physiology. Based on this data, the role of GERD in DES has been overemphasized. To establish causation and assess the clinical significance of GERD, future studies should investigate potential differences in treatment response between DES patients with and without reflux. Table 1. - Patient characteristics, presenting symptoms, and manometric differences in patients with confirmed reflux-DES vs non-reflux DES Characteristics n (%)/mean (sd)/median [IQR] R-DES NR-DES N 32 36 Demographics P-value Age at Time of Manometry 60.84 (12.70) 56.61 (14.48) 0.207 BMI 26.93 (5.64) 30.33 (5.22) 0.012* Sex 1 Male 13 (40.6) 14 (38.9) Race/Ethnicity 0.0687 White (Non-Hispanic) 0 16 (50.0) 18 (50.0) Black (Non-Hispanic) 1 2 (6.3) 4 (11.1) Asian 2 1 (3.1) 2 (5.6) Other (Non-Hispanic) 4 8 (25.0) 5 (13.9) Hispanic 3 4 (12.5) 7 (19.4) Medical History History of Tobacco Use 14 (43.8) 11 (30.6) 0.382 History of Alcohol Use 18 (56.2) 19 (52.8) 0.966 Current PPI use 25 (78.1) 33 (91.7) 0.218 Diabetes 4 (12.5) 4 (11.1) 1 Reason HRM Performed 0.603 Dysphagia/Non-Cardiac Chest Pain Symptoms 4 (12.5) 5 (13.9) GERD Testing 24 (75.0) 28 (77.8) Both Dysphagia Symptoms and GERD Testing 4 (12.5) 2 (5.6) Other atypical symptoms 0 (0) 1 (2.8) Presenting Symptoms Abdominal pain 8 (25.0) 13 (36.1) 0.432 Belching 4 (12.5) 4 (11.1) 1 Chest pain 4 (12.5) 6 (16.7) 0.739 Choking 3 (9.4) 4 (11.1) 1 Cough 13 (40.6) 9 (25.0) 0.783 Dysphagia 13 (40.6) 10 (27.8) 0.311 Globus sensation 9 (28.1) 11 (30.6) 1 Heartburn 20 (62.5) 26 (72.2) 0.551 Nausea/vomiting 7 (21.9) 9 (25.0) 0.783 Regurgitation 15 (46.9) 11 (30.6) 0.214 pH Testing Symptom Correlation Symptom Index > 50 10 (45.5) 5 (26.3) 0.33 Symptom Association Probability > 95 5 (21.7) 4 (19.0) 1 Manometry Findings Presence of Hiatal Hernia 29 (90.6) 31 (86.1) 0.842 Size of Hiatal Hernia (cm) 2.50 [1.50, 3.90] 2.3 [1.60, 3.95] 0.929 LES Basal Pressure (mmHg) 23.70 (14.78) 31.38 (18.74) 0.07 LES Residual Pressure (mmHg) 12.92 (7.50) 16.72 (10.70) 0.098 Percent Peristaltic (%) 55 [40.00, 100.00] 81 [50.00, 100.00] 0.328 Incomplete Bolus Clearance (%) 80.00 [40.00, 100.00] 60.00 [27.50, 90.00] 0.290 Mean Distal Contractile Integral 1765.85 (±1213.76) 1522.49 (±963.03) 0.180