Background/Purpose: Skeletal myopathy in systemic sclerosis (SSc) is associated with poor outcomes such as disability.  The spectrum of muscle histopathology of weak SSc patients is heterogeneous. The purpose of this study was to determine the clinical phenotype and outcome of those with predominant fibrosis on muscle biopsy and compare them to those with inflammatory and/or necrotizing muscle biopsies. 

Methods: This retrospective, cross-sectional study included SSc patients with muscle weakness and muscle biopsies available for review. Biopsies were assessed for individual pathologic features including inflammation, necrosis, and fibrosis as previously described (1). Biopsies were assigned a histopathologic category of “inflammatory myopathy” if they had inflammation and/or necrosis with or without fibrosis.  Biopsies with predominant fibrosis and no inflammation or necrosis were designated as “fibrosing myopathy”.  Clinical data including SSc subtype, disease duration, serum creatine kinase (CK) levels, electromyography (EMG), autoantibody profile, and survival (including Kaplan Meier curves) were compared between the two groups.

Results: 47 biopsies from weak SSc patients were available for review; 8 had fibrosing myopathy, 28 had inflammatory myopathy, and 11 could not be classified as either of these.  Survival analyses demonstrated that patients with fibrosing myopathy had a statistically significant higher death rate (5 of 8; 62.5%) compared to those with inflammatory myopathy (4 of 28; 14.3%; p=0.01) (Figure 1). The mean time to death from muscle biopsy was 0.28 ± 0.19 years in those with fibrosing myopathy compared to 2.50 ± 1.6 years with inflammatory myopathy (p=0.01).  Although not reaching statistical significance, compared to those with inflammatory myopathy, SSc patients with fibrosing myopathy were more likely to have the diffuse SSc subtype (87% vs. 64%, p=0.21), African-American race (62.5% vs. 35.7%; p=0.17), shorter disease duration since first non-Raynaud’s symptoms (2.31 + 1.97 years vs. 2.86 ± 3.4 years; p=0.58), and lower FVC (55.5 ± 31.9 vs. 66.4 ± 17.6; p=0.23). There was also a trend for patients with fibrosing myopathy to have lower CK values (516 ± 391 vs. 2477 ± 3511, p=0.13) and more frequent non-irritable myopathy on EMG (57.1% vs. 34.7%, p=0.27). Anti-Scl-70 antibodies were found in 25% (2 of 8) of patients with fibrosing myopathy and only 4% (1 of 28) of those with inflammatory myopathy (p=0.14). 

Conclusion: SSc patients with muscle weakness and a fibrosing myopathy have markedly increased mortality compared to those with inflammatory myopathy.

Figure 1: Kaplan-Meier survival estimates comparing SSc patients with fibrosing myopathy vs. inflammatory myopathy References

 ADDIN ZOTERO_BIBL {"custom":[]} CSL_BIBLIOGRAPHY 1. Paik JJ, Wigley FM, Lloyd TE, Corse AM, Casciola-Rosen L, Shah AA, et al. Spectrum of Muscle Histopathologic Findings in Forty-Two Scleroderma Patients With Weakness. Arthritis Care Res 2015;67:1416–1425.