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Introduction: Previously, we discovered similar esophageal gene expression patterns in patients with systemic sclerosis (SSc) and eosinophilic esophagitis (EoE) where eosinophil/mast cell-targeted therapies are beneficial. Because SSc and EoE patients experience similar esophageal symptoms, we hypothesized that eosinophil/mast cell-directed therapy may potentially benefit SSc patients. Herein, we determine the association between esophageal mast cell quantities, gene expression and clinical parameters in order to identify SSc patients who may benefit from eosinophil/mast cell-directed therapy., Methods: Esophageal biopsies from SSc patients and healthy participants were stained for tryptase, a mast cell marker, and associations with relevant clinical parameters including 24h esophageal pH testing were assessed. Intra-epithelial mast cell density was quantified by semi-automated microscopy. Microarray data were utilized for functional and gene set enrichment analyses and to identify intrinsic subset (IS) assignment, an SSc molecular classification system that includes inflammatory, proliferative, limited and normal-like subsets., Results: Esophageal biopsies from 40 SSc patients (39 receiving proton pump inhibition) and eleven healthy participants were studied. Mast cell numbers in both the upper esophagus (r s = 0.638, p = 0.004) and the entire (upper + lower) esophagus (r s = 0.562, p = 0.019) significantly correlated with acid exposure time percentage. The inflammatory, fibroproliferative, and normal-like ISs originally defined in skin biopsies were identified in esophageal biopsies. Although esophageal mast cell numbers in SSc patients and healthy participants were similar, gene expression for mast cell-related pathways showed significant upregulation in the inflammatory IS of SSc patients compared to patients classified as proliferative or normal-like., Discussion: Esophageal mast cell numbers are heterogeneous in SSc patients and may correlate with acid exposure. Patients with inflammatory IS profiles in the esophagus demonstrate more tryptase staining. Mast cell targeted therapy may be a useful therapeutic approach in SSc patients belonging to the inflammatory IS, but additional studies are warranted., Competing Interests: Declaration of conflicting interests Paul Bryce is currently an employee of Sanofi-Regeneron, but his involvement in this study is exclusively related to his prior employment at Northwestern University. The remaining authors report no conflicts of interest.

Patients with systemic sclerosis often seek information regarding complementary and nutrition-based therapy. Some study results have shown that vitamins D and E, probiotics, turmeric, l-arginine, essential fatty acids, broccoli, biofeedback, and acupuncture may be beneficial in systemic sclerosis care. However, large randomized clinical trials have not been conducted. This review summarizes current data regarding various complementary therapies in systemic sclerosis and concludes with recommendations., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Purpose: To evaluate the utility of cardiac magnetic resonance (CMR) T1 mapping in early systemic sclerosis (SSc) and its association with skin score., Methods: Twenty-four consecutive patients with early SSc referred for cardiovascular evaluation and 12 controls without SSc were evaluated. All patients underwent cine, T1 mapping, and late gadolinium enhanced (LGE) CMR imaging. T1 mapping indices were compared between SSc patients and controls (extracellular volume fraction [ECV], gadolinium partition coefficient [λ], pre-contrast T1, and post-contrast T1). The association between T1 mapping parameters and the modified Rodnan skin score (mRSS) was determined., Results: There were no significant differences in cardiac structure/function between SSc patients and controls on cine imaging, and 8/24 (33%) SSc patients had evidence of LGE (i.e., focal myocardial fibrosis). Of the T1 mapping parameters (indices indicative of diffuse myocardial fibrosis), ECV differentiated SSc patients from controls the best, followed by λ, even when the eight SSc patients with LGE were excluded. ECV had a sensitivity and specificity of 75% and 75% for diffuse myocardial fibrosis (optimal abnormal cut-off value of >27% [area under ROC curve=0.85]). In the 16 patients without evidence of LGE, each of the 4 CMR T1 mapping parameters (ECV, λ, Pre-T1 and Post-T1) correlated with mRSS (R=0.51-0.65, P=0.007-0.043), indicating a correlation between SSc cardiac and skin fibrosis., Conclusions: The four T1 mapping indices are significantly correlated with mRSS in patients with early SSc. Quantification of diffuse myocardial fibrosis using ECV should be considered as a marker for cardiac involvement in SSc clinical studies., Competing Interests: Conflict of interest DL (research grant – Abbott Laboratories; advising, consulting –Gilead Sciences, Inc); MH (consulting – Bayer HealthCare Pharmaceuticals, Inc, Sanofi Aventis Pharmaceuticals); JV (advising, consulting -Amira Pharmaceuticals); JCC (advising, consulting - Astellas Pharma, Inc., Bayer HealthCare Pharmaceuticals, Inc., Lantheus Medical Imaging, Inc.) RS, MMS, AA, BCB, AT, KK, JL, MC, KA and SJS declare no competing interests