Managing gastrointestinal manifestations in systemic sclerosis, a mechanistic approach

Abstract

Introduction: Systemic sclerosis (SSc) is a connective tissue disease with heterogeneous presentation. Gastrointestinal (GI) complications of SSc are characterized by esophageal reflux, abnormal motility, and microbiome dysbiosis, which impact patient quality of life and mortality. Preventative therapeutics are lacking, with management primarily aimed at symptomatic control.

Areas covered: A broad literature review was conducted through electronic databases and references from key articles. We summarize the physiology of gastric acid production and GI motility to provide context for existing therapies, detail the current understanding of SSc-GI disease, and review GI medications studied in SSc. Finally, we explore new therapeutic options. We propose a management strategy that integrates data on drug efficacy with knowledge of disease pathophysiology, aiming to optimize future therapeutic targets.

Expert opinion: SSc-GI complications remain a challenge for patients, clinicians, and investigators alike. Management presently focuses on treating symptoms and minimizing mucosal damage. Little evidence exists to suggest immunosuppressive therapy halts progression of GI involvement or reverses damage, leaving many unanswered questions about the optimal clinical approach. Further research focused on identifying patients at risk for GI progression, and the underlying mechanism(s) that drive disease will provide opportunities to prevent long-term damage, and significantly improve patient quality of life.

Keywords: Systemic sclerosis; gastrointestinal; mechanism; scleroderma; therapies.

Figure 1.

A Proposed Treatment Algorithm for GI Symptoms in SSc, Based on Available Study Data and Expert Opinion

Figure 2.

Known Mechanistic Targets for GI Symptom Therapeutics and Applications for SSc

Figure 3.

Identified Challenges in the Management of Gastrointestinal Symptoms in Systemic Sclerosis