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
• scleroderma
• therapies
• mechanism

Article highlights

• Gastroesophageal reflux is the most common SSc-GI symptom and is a consequence of dysmotility, with management primarily focused on acid suppression before advancing to prokinetic options, and surgery can be considered in select patients.

• SSc dysmotility is heterogeneous and may involve any component of the GI tract, with therapeutic decision-making often dependent on the specific site efficacy of medications.

• SSc-GI dysbiosis is common and may be a consequence of underlying dysmotility or treatments, versus an inciting pathologic mechanism; antibiotic regimens such as rifaximin show efficacy in treatment of bacterial overgrowth in SSc, with emerging therapeutics such as probiotics and fecal microbiota transplantation showing promise.

• Novel SSc-GI therapies such as intravenous immunoglobulin, transcutaneous electric nerve stimulation, and the vibrating capsule show potential in treating specific GI complications, with a current need to identify appropriate therapeutic candidates.

Declaration of interest

Z McMahan is a consultant for Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by NIH (1 R01 AR081382-01A1).