Background/Purpose: Scleromyositis (SM) is an emerging subset of autoimmune myositis (AIM) in patients with features of systemic sclerosis (SSc). SM patients may present without characteristic SSc skin thickening and without known SSc autoantibodies. We previously reported that SM was characterized by marked capillary basement membrane (BM) reduplication, even in patients with mild SSc features. The objective of this study was to confirm this histopathological finding in an independent cohort.

Methods: A standardized review of an independent cohort of SM cases and AIM controls was performed by 2 reviewers. In the absence of a gold standard, SM cases were selected based on clinicoserological features by a consensus of ≥2 experts. All stains recommended by the European NeuroMuscular Center (ENMC) for histopathological assessment of inflammatory muscle biopsy were performed. Muscle biopsies from SM cases and AIM controls were categorized using the ENMC criteria. Collagen IV immunofluorescence was performed to assess endomysial capillary abnormalities (dropout and/or mural thickening and/or luminal dilation) and electron microscopy to examine capillaries for BM reduplication (mild, 2-3 layers; marked, ≥4 layers).

Results: Twenty-four SM cases and 17 AIM controls (4 dermatomyositis (DM), 5 anti-HMGCR+ immune-mediated necrotizing myopathy (IMNM), 5 inclusion body myositis (IBM) and 3 antisynthetase syndrome) were reviewed. SM cases were predominantly females (63%) and mean age at diagnosis was 58 years (range, 27-81). Proximal muscle weakness was present in 74% of SM cases and mean CK level was 2561 IU/L (range, 180-9239). Eighty-three percent (19/23) of SM cases fulfilled the ACR/EULAR SSc criteria at the time of myositis diagnosis. SSc features supporting the diagnosis of SM in the 4 remaining cases included: Raynaud’s phenomenon (n=4), positive ANAs and/or SSc-associated autoantibodies (n=3), SSc-type nailfold capillaroscopy (n=3), interstitial lung disease (n=2) and puffy fingers (n=1). Using the ENMC criteria, SM cases were mainly categorized as IMNM (54%), non-specific myopathic changes (17%), non-specific myositis (13%), unclassifiable (8%), IBM (4%) or polymyositis (4%). When using complementary techniques for capillary assessment, immunofluorescence identified abnormal capillaries in 95% (20/21) of SM cases vs 56% (5/9) of controls (p=0.0195), and electron microscopy demonstrated capillary BM reduplication in 83% of SM cases vs 35% of controls (p=0.0028). This difference in BM reduplication between SM and controls was even higher when only marked BM reduplication (≥4 layers) was considered (71% of SM vs 12% of controls, p=0.0003). In SM patients who did not fulfill the ACR/EULAR criteria for SSc, 100% (4/4) showed BM reduplication; and in SM patients without known SSc autoantibodies, 83% (5/6) showed BM reduplication.

Conclusion: In this validation study, we confirmed that marked BM reduplication is the hallmark histopathological feature of SM. Ultrastructural evaluation of muscle capillaries is useful to support an accurate diagnosis of SM.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/marked-capillary-basement-membrane-reduplication-is-the-hallmark-histopathological-feature-of-scleromyositis/