Background/Purpose: Scleromyositis (SM) is an emerging subgroup of autoimmune myositis (AIM) associated with features of systemic sclerosis (SSc). Muscle biopsy studies are sparse and have suggested that SM is heterogeneous. Whether there is a distinct pathological signature remains uncertain. SSc is associated with a prominent vasculopathy. The aim of this study was to explore whether a distinct vasculopathic pattern is associated with SM as compared to other AIM.

Methods: A systematic review of SM muscle biopsies and AIM controls was performed by 2 reviewers. In the absence of gold standard, SM clinical diagnosis was based on expert opinion (consensus of ≥2 experts). Reviewers were blinded to the clinical diagnosis/serological status and used a pre-specified protocol including all stains recommended by the ENMC for the pathological diagnosis of AIM, and collagen IV immunofluorescence for endomysial capillary abnormalities (dropout and/or mural thickening and/or luminal dilation). Examination of capillaries was also done by electron microscopy (EM) for the presence of marked basement membrane (BM) reduplication (≥5 layers) and endothelial abnormalities.

Results: 31 SM cases and 18 AIM controls (4 dermatomyositis, 5 immune-mediated necrotizing myopathies (IMNM, all anti-HMGCR+), 5 inclusion body myositis (IBM), and 4 antisynthetase syndrome) were included. SM patients were predominantly females (86%) and mean age at muscle biopsy was 55.6±13.1 years. Myopathic features at presentation were: proximal weakness in 86% of patients and mean CK elevation of 1596±1510 IU/L. 71% of patients fulfilled the ACR/EULAR SSc criteria at myositis diagnosis. SSc features leading to the diagnosis of SM in the remaining 8 patients included: Raynaud phenomenon (n=7), positive ANAs and/or SSc-associated autoantibodies (n=7), interstitial lung disease (n=5), SSc nailfold capillaroscopy (n=3), sclerodactyly (n=1) and puffy fingers (n=1). Capillary BM reduplication was observed in 68% (n=21) of SM muscle biopsies compared to 11% of AIM controls (mildly observed in 2 IBM) (p< 0.001). Marked capillary BM reduplication was only observed in SM biopsies (55%, n=17). Of the SM patients without BM reduplication, all but one presented capillary abnormalities on immunofluorescence and/or endothelial abnormalities on EM. Using the ENMC pathological criteria for AIM, our SM cases would have been most frequently classified as IMNM (32%) or non-specific myositis (32%). In the subset of SM cases with an IMNM-like phenotype, marked BM reduplication and/or other ultrastructural capillary abnormalities were observed in all SM cases and none of the IMNM controls. No cases of dermatomyositis showed marked BM reduplication.

Conclusion: SM is associated with endomysial capillary BM reduplication, a distinct ultrastructural vasculopathic feature compared to other AIM.  SM is a frequent mimicker of IMNM on muscle biopsy and should be ruled out by ultrastructural examination of capillaries in patients negative for anti-SRP or anti-HMGCR autoantibodies. The identification of marked BM reduplication may improve early identification of SM, especially in those presenting without SSc skin involvement.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/scleromyositis-is-associated-with-distinct-muscle-vasculopathic-features/