Gastrointestinal tract involvement in systemic sclerosis: The roles of diet and the microbiome.

BACKGROUND: Alterations in gastrointestinal (GI) microbial composition have been reported in patients with systemic sclerosis (SSc). However, it is unclear to what degree these alterations and/or dietary changes contribute to the SSc-GI phenotype. OBJECTIVES: Our study aimed to 1) evaluate the relationship between GI microbial composition and SSc-GI symptoms, and 2) compare GI symptoms and GI microbial composition between SSc patients adhering to a low versus non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet. METHODS: Adult SSc patients were consecutively recruited to provide stool specimens for bacterial 16S rRNA gene sequencing. Patients completed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0) and the Diet History Questionnaire (DHQ) II and were classified as adhering to a low or non-low FODMAP diet. GI microbial differences were assessed using three metrics of alpha diversity (species richness, evenness, and phylogenetic diversity), as well as beta diversity (overall microbial composition). Differential abundance analysis was performed to identify specific genera associated with SSc-GI phenotype and low versus non-low FODMAP diet. RESULTS: Of the 66 total SSc patients included, the majority were women (n = 56) with a mean disease duration of 9.6 years. Thirty-five participants completed the DHQ II. Increased severity of GI symptoms (total GIT 2.0 score) was associated with decreased species diversity and differences in GI microbial composition. Specifically, pathobiont genera (e.g., Klebsiella and Enterococcus) were significantly more abundant in patients with increased GI symptom severity. When comparing low (N = 19) versus non-low (N = 16) FODMAP groups, there were no significant differences in GI symptom severity or in alpha and beta diversity. Compared with the low FODMAP group, the non-low FODMAP group had greater abundance of the pathobiont Enterococcus. CONCLUSION: SSc patients reporting more severe GI symptoms exhibited GI microbial dysbiosis characterized by less species diversity and alterations in microbial composition. A low FODMAP diet was not associated with significant alterations in GI microbial composition or reduced SSc-GI symptoms; however, randomized controlled trials are needed to evaluate the impact of specific diets on GI symptoms in SSc.

Current advances in the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a rare, systemic autoimmune disease of unknown etiology. Among the systemic rheumatic diseases, SSc carries the highest mortality, in part due to the historical lack of disease modifying therapies. Recently, landmark randomized controlled trials (RCTs) have been conducted that have illustrated the heterogeneous nature of SSc and furthered our understanding of the key inflammatory and fibrotic pathways involved in SSc pathogenesis. Although SSc affects various organ systems, RCTs have focused on investigating treatments for diffuse cutaneous sclerosis (dcSSc) and interstitial lung disease (ILD). While recent RCTs for dcSSc have failed to demonstrate a treatment benefit, the outcomes of two RCTs led to the approval of two novel therapies for SSc-ILD: nintedanib and tocilizumab. This review summarizes the salient outcome data from recent SSc trials within a practical clinical framework and points out gaps in knowledge that may help inform the design of future SSc studies.

Sudden Cardiac Death due to Coronary Artery Vasculitis in a Patient with Relapsing Polychondritis.

Relapsing polychondritis (RP) is a systemic autoimmune disease characterized by relapsing and remitting inflammation of the cartilaginous structures of the ears, nose, tracheobronchial tree, and joints. Diagnosis is challenging due to the heterogeneity of clinical manifestations, the relapsing and remitting nature of the disease, the presence of coexistent diseases in at least one-third of patients, and the lack of a diagnostic blood test. Although RP-associated cardiac disease is the second most common cause of death behind tracheobronchial complications, coronary artery vasculitis is rare. This report describes a case of sudden cardiac death due to vasculitis affecting the coronary arteries in a patient with RP. The pathologic findings included obliterative coronary arteritis with plasma cells and storiform fibrosis, features suggesting that IgG4-related disease (IgG4-RD) may have contributed to the patient's cardiac disease. The literature on vasculitis and cardiac disease in RP and the possible role of IgG4-RD in this setting is also reviewed. The primary take-home message from this case report is the importance of frequent screening for cardiac disease, regardless of symptoms, in patients with RP. In addition, considering the diagnosis of IgG4-RD in some cases thought to be RP may also be warranted.