Tubuloreticular inclusions in juvenile dermatomyositis: a diagnostically useful marker?

Abstract

Introduction: Juvenile Dermatomyositis (JDM) is a rare life threatening disease affecting children. Symptoms include severe proximal muscle weakness and characteristic skin rashes. Vascular pathology is often a key finding in patients; patterns of pathology from biopsies of muscle and skin support the diagnosis. A common finding in JDM biopsies is the presence of tubuloreticular inclusions (TRI) in blood vessel endothelial cells in muscle and the overlying clinically-unaffected skin detected by electron microscopy (EM). These are tubule-like structures of unknown origin and are often found in the cytoplasm of endothelial cells.The aim of this study was to determine the frequency and specificity of TRI in JDM biopsies compared to muscle biopsies investigated for other diseases in children. Material(s) and Method(s): The UK JDM Biomarker and Cohort Study (JDBCS) has the largest JDM cohort with linked samples and biopsies, worldwide (n = 463, biopsies n = 135). We examined the EM pathology reports from 40 JDM biopsies where an EM report was available, and from 500 muscle biopsies investigated for other conditions, for reports of TRI in blood vessel endothelial cells. Result(s): TRI were demonstrated in blood vessel endothelial cells in 80% of JDM muscle biopsies (n = 40) and in the overlying skin in 78% of cases (n = 32) where this tissue was available. In contrast no reports of TRI in vessel endothelial cells were found in muscle biopsies investigated for other pathologies in children (n > 500). Conclusion(s): The high number of JDM muscle biopsies with identified TRI compared to control biopsies suggests that TRI are a highly specific marker of JDM pathology and so are useful in supporting a diagnosis of JDM in patients. TRI are suggested to be a biomarker of type1 interferon (IFN) exposure1. Type 1 IFN gene and chemokine signature is thought to be associated with JDM muscle pathology2and clinical features3. Therefore the frequency of these structures in muscle biopsies may suggest stratified approaches to treatment with IFN blockade in subgroups of patients.