To present a case of severe immune mediated necrotizing myositis in a patient with autoantibodies to HGMCR, MDA-5, CADM-140, NXP-2, and RNP without dermatologic involvement that was minimally responsive to intravenous immune globulin (IVIG) requiring cyclophosphamide.

Immune-mediated inflammatory myopathies are complex multisystem diseases with a wide spectrum of manifestations. Myositis-specific autoantibodies have been identified and associated with distinct clinical phenotypes. Anti-HMGCR has been representative of immune-mediated necrotizing myopathy, while anti-MDA-5 has been associated with prominent mucocutaneous features and lung involvement leading to a rapidly progressive interstitial lung disease (ILD). Coexistence of anti-HMGCR and anti-MDA-5 is rare and prior cases had typical dermatomyositis skin findings and interstitial lung disease.

A 43-year-old female with a history of hypothyroidism presented with seven months of progressive proximal muscle weakness requiring a wheelchair and worsening shortness of breath. On exam she had no skin findings, severe proximally predominant weakness, with normal reflexes and sensation. Her creatine kinase was 11,543 units/L. Chest/abdomen/pelvis computed tomography showed no malignancy or signs of interstitial lung disease. Right vastus lateralis muscle biopsy showed widespread myofiber necrosis without a perifascicular pattern and patchy lymphocytic inflammation. Myositis panel was positive for MDA-5, CADM-140, NXP-2, HMGCR, and RNP autoantibodies. She was treated with IVIG and 1 gram of methylprednisolone for 5 days with minimal improvement. The patient had worsening shortness of breath and swallowing, and she was treated with 1 gram of cyclophosphamide. Her swallowing and shortness of breath improved, and she was discharged to acute rehab.

Anti-HMGCR and anti-MDA-5 antibodies can be seen in necrotizing myositis without dermatologic involvement and ILD. A full myositis panel should be tested when there is a high suspicion for a necrotizing myopathy. Further research is needed to assess if more aggressive immunotherapy is required in patients with anti-HMGCR and multiple myositis-specific autoantibodies like anti-MDA-5.