Scleroderma-polymyositis overlap syndrome versus idiopathic polymyositis and systemic sclerosis: a descriptive study on clinical features and myopathology

Abstract

Introduction: The objective was to characterize the clinical and myopathologic features of patients with scleroderma-polymyositis (SSc-PM) overlap compared with a population of patients with systemic sclerosis (SSc) and polymyositis (PM).

Methods: A three-way comparison of patients with SSc-PM overlap (n = 25) with patients with SSc (n = 397) and PM (n = 40) on clinical and myopathologic features and causes of death. One neuropathologist blinded for the diagnosis evaluated all recent available muscle biopsies. Biopsies were scored for presence of inflammation, necrotic muscle fibers, rimmed vacuoles, fibrosis, and immunohistochemical staining. Clinical or myopathologic characteristics were compared by using the χ(2) test or one-way analysis of variance (ANOVA).

Results: The prevalence of SSc-PM overlap in the Nijmegen Systemic Sclerosis cohort was 5.9%. The mortality was 32% (eight of 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 with SSc (49%) and PM (53%). SSc or myositis-specific antibodies were nearly absent in the SSc-PM group. In almost all biopsies (96%) of SSc-PM patients, necrotic muscle fibers were present, which was significantly increased compared with PM patients (P = 0.02).

Conclusions: Patients with SSc-PM have increased prevalence of pulmonary fibrosis and cardiac disease as the cause of death compared with patients with SSc and PM . In addition, we found that necrotizing muscle fibers with inflammation characterize SSc-PM overlap in muscle biopsies. Further research should focus on underlying mechanisms causing necrosis, inflammation, and fibrosis and their relation to pulmonary involvement and mortality in patients with SSc-PM overlap.

Figure 1

Histopathologic muscle-biopsy images of SSc-PM overlap patient versus PM patient. Left side (A, C, E): SSc-overlap patient. Right side (B, D, F): PM patient. (A) Hematoxylin & eosin (H&E) stain; upper marker, necrosis; lower marker, lymphocytic infiltrate; (B) H&E stain; marker, lymphocytic infiltrate; (C) MAC stain; markers, MAC upregulation; (D) MAC stain, no upregulation; (b v 02D7; (E) MHC class I stain, sarcolemmal MHC class I upregulation; (F) MHC class I stain, sarcolemmal and diffuse cytoplasmic MHC class I upregulation.