This study aimed to characterize the clinical and myopathological features of patients with scleroderma-polymyositis (SSc-PM) overlap syndrome compared to a population of patients with systemic sclerosis (SSc) and polymyositis (PM). A three-way comparison of clinical and myopathological features and causes of death was carried out between patients with SSc-PM overlap syndrome (n = 25), patients with SSc (n = 397) and patients with PM (n = 40). A neuropathologist blinded for the diagnosis evaluated all recent available muscle biopsies. Biopsies were scored for the presence of inflammation, necrotic muscle fibers, rimmed vacuoles, fibrosis and immunohistochemical staining. Clinical or myopathological characteristics were compared using the Chi-square test or one-way ANOVA. The prevalence of SSc-PM overlap in the Nijmegen Systemic Sclerosis cohort was 5.9%. The mortality rate was 32% (8/25) in SSc-PM, of which half was related to cardiac diseases. The prevalence of pulmonary fibrosis was significantly increased in SSc-PM (83%) (P = 0.04) compared to SSc (49%) and PM (53%). SSc or myositis specific antibodies were nearly absent in SSc-PM group. In almost all biopsies (96%) of SSc-PM patients necrotic muscle fibers were present, which was significantly increased compared to PM patients (P = 0.02). Patients with SSc-PM have an increased prevalence of pulmonary fibrosis and cardiac disease as a cause of death compared to patients with SSc and PM. Furthermore, it was found that necrotizing muscle fibers with inflammation characterize SSc-PM overlap in muscle biopsies. Further research should focus on revealing the underlying mechanisms that cause necrosis, inflammation and fibrosis and their relationship to pulmonary involvement and mortality in patients with SSc-PM overlap.
