Immune myopathies with perimysial pathology

Objective Immune myopathies with perimysial pathology (IMPP) have a combination of damage to perimysial connective tissue and muscle fiber necrosis, more prominent near the perimysium. We studied the clinical and laboratory correlates of patients with pathologically defined IMPP. Methods This is a retrospective chart and pathology review of 57 consecutive patients with IMPP myopathology and, for comparison, 20 patients with dermatomyositis with vascular pathology (DM-VP). Results Compared with DM-VP, IMPP patients more commonly had interstitial lung disease (ILD) (p < 0.01), Raynaud phenomenon (p < 0.05), mechanic’s hands (p < 0.05), arthralgias (p < 0.001), and a sustained response to immunomodulatory therapy (p < 0.05), and less frequently had a concurrent malignancy (p < 0.01). IMPP patients had higher serum creatine kinase values (p < 0.05), more frequent serum Jo-1 (p < 0.03) or SSA/SSA52 autoantibodies (p < 0.05), and less frequent antinuclear antibodies (p < 0.01). IMPP patients with serum Jo-1/antisynthetase antibodies were more likely to have ILD (p < 0.05) and inflammatory arthritis (p < 0.05) than IMPP patients without these antibodies. Conclusions IMPP myopathology is associated with an increased risk of ILD, Raynaud phenomenon, mechanic’s hands, and inflammatory arthritis when compared with another immune myopathy (DM-VP). IMPP patients require regular screening for ILD, particularly those with antisynthetase antibodies. The absence of myositis-specific autoantibodies in a large percentage of IMPP patients emphasizes the important role for myopathology in identifying patients at higher risk of severe comorbid conditions such as ILD. From the Department of Neurology, Washington University School of Medicine, St. Louis, MO. Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was funded by the authors. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. 1 Acquired immune and inflammatory myopathies (IIMs) are a heterogeneous group of disorders. Classification schemes have been based on clinical, autoantibody, or myopathologic features. Serum antibodies to aminoacyl-tRNA synthetases are associated with a multisystem syndrome that includes IIM. Clinical manifestations include myopathy, interstitial lung disease (ILD), arthritis, Raynaud phenomenon, and skin rash. The commonest antisynthetase antibody, anti-Jo-1, is directed against histidyl tRNA synthetase. Myopathology in patients with anti-Jo-1 antibodies includes damage to perimysial connective tissue and muscle fibers. Perimysial connective tissue pathology includes damaged structures with fragmentation and scattered histiocytic cells. Muscle fiber pathology includes necrosis and regeneration, more prominent in regions neighboring the perimysium.We have termed myopathies with this combined pattern of damage, immune myopathies with perimysial pathology (IMPP). IMPP also occurs with serum antibodies to hydroxy-methyl-glutarylcoenzyme A reductase (HMGCR), a nonaminoacyl-tRNA synthetase antigen. Other patients with IMPP have no associated myositis-specific antibodies (MSA). This study examined clinical and laboratory features of a cohort of consecutive patients with IMPP evaluated at our institution. We compared IMPP patients with a cohort of patients with a different immune myopathy syndrome, dermatomyositis with vascular pathology (DM-VP). DM-VP differs pathologically from IMPP, as it is a myovascular disorder. Muscle fiber changes are generally atrophy, rather than the necrosis seen in IMPP. Our results show that IMPP is associated with myopathy syndromes having multisystem features involving muscle, lungs, skin, and joints.