Gastrointestinal histology of systemic sclerosis: A systematic review

Objective: To systematically review and synthesize the histological findings of gastrointestinal (GI) tissue in patients with systemic sclerosis (SSc), aiming to clarify the role of fibrosis and other pathological processes in SSc-related GI disease. Methods: A comprehensive literature search was conducted across MEDLINE (OVID), Web of Science, and Cochrane Library databases for studies published in English from 1960 to 2025. Inclusion criteria required studies to report qualitative histological findings from GI tissue (esophagus to anorectum) in adult SSc patients, excluding those with overlapping autoimmune diseases or malignancy. Data extraction and appraisal were performed independently by multiple reviewers. Results: Of 1697 screened articles, 36 met inclusion criteria. Histological analysis revealed that fibrosis, while common, was not universal nor evenly distributed across GI layers. The mucosa predominantly exhibited in f lammatory infiltrates (mast cells, macrophages, lymphocytes), villous atrophy, and less frequent fibrosis. Sub mucosal findings were inconsistent, with variable reports of vascular changes and nerve plexus degeneration. The muscularis layer showed near-universal smooth muscle atrophy and variable fibrosis, with decreased density of interstitial cells of Cajal (ICC) in some studies. Neuronal and mitochondrial pathology were underreported. Conclusion: GI pathology in SSc is multifaceted, involving inflammation, cellular degeneration, neuronal dysfunction, and smooth muscle atrophy, with fibrosis as a variable feature. Standardization of histological reporting and further ultrastructural studies are needed to elucidate mechanisms and guide future research and therapeutic strategies