Background/Purpose: The macrophage activation is elevated in systemic sclerosis (SSc) patients, and is implicated in pathogenesis of tissue inflammation, fibrosis, and the development of skin disease and interstitial lung disease. The gastroesophageal manifestations are common in SSc, with significant motility and mucosal complications. In this study, we aimed to investigate the potential influence of macrophages in SSc esophagus.

Methods: In this single-center observational study, we prospectively enrolled patients with SSc and primary gastroesophageal reflux disease (GERD) patients to the study. The SSc patients fulfilled the 2013 ACR/EULAR Classification Criteria. The primary GERD patients were examined by gastroenterologist and rheumatologist by clinical and serology tests to exclude possible autoimmune diseases and other structural gastrointestinal disorders.

The patients underwent a series of esophageal and gastric examinations including upper gastroendoscopy, high-resolution esophageal manometry, and middle-portion esophageal endoscopic mucosal biopsy. The erosive esophagitis was graded with Los Angeles classification and the diagnosis of motility disorder was classified according to Chicago Classification version 4.0.

The esophageal biopsy specimens were examined using light microscopy with hematoxylin-eosin stain, and immunohistochemical stains with CD117, Desmin, CD3, CD20, and CD68.

The statistical significance was calculated using Fisher’s exact test for binomial parameters and Wilcoxon rank sum exact test for continuous and categorical data.

Results: From September 2021 to March 2023, 22 SSc patients and 6 primary gastroesophageal reflux disease patients completed the study. The median ages and female sex were similar across both groups. The rates of erosive esophagitis (59% vs. 33%, p = 0.4) and the LA gradings (p = 0.6%) were comparable. On immunohistochemical stains, the SSc patients exhibited increased T cell (100% vs. 50%, p = 0.006) and macrophage (68% vs. 0%, p = 0.008) infiltrations.

In SSc patients, the presence of esophageal macrophage infiltration was not associated with age, female sex, GERD and dysphagia symptoms, the proportion of the absent contractility on manometry, the interstitial lung disease, the functional vital capacity, or the diffusion of carbon monoxide. However, the macrophage infiltration is associated with a decreased upper esophageal sphincter relaxation pressure (7.7 vs. 11.7 mmHg, p = 0.007) and numerically higher rates of erosive esophagitis (73% vs. 29%, p = 0.074.)

Conclusion: In this study, we found a higher proportion of T cell and macrophage infiltrations in SSc patients compared with primary GERD individuals, irrespective of the mucosal complications. The macrophage infiltration in SSc patients was associated with decreased esophageal sphincter pressure and numerically higher incidence of erosive esophagitis. The observation supported the pathological role of macrophages in SSc and indicated its significance in developing esophageal mucosal and functional complications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increase-in-macrophage-infiltration-in-scleroderma-esophageal-mucosa-is-associated-with-motility-and-mucosal-complications/