Necrotizing dermatomyositis (NDM) represents a rare and severe inflammatory myopathy characterized by clinical features of dermatomyositis (DM) with histopathologic evidence of myofiber necrosis and minimal inflammatory infiltrates. Immune-mediated necrotizing myopathy is classically associated with anti-signal recognition particle (SRP) and anti-HMG-CoA reductase (HMGCR) antibodies; however, seronegative cases occur and may overlap with DM-specific autoantibodies such as anti-nuclear matrix protein 2 (anti-NXP2). Coexisting metabolic conditions, including hypothyroidism, may obscure the diagnosis. We report a 60-year-old woman with Hashimoto’s thyroiditis who developed progressive proximal weakness and markedly elevated creatine kinase (CK) levels initially attributed to uncontrolled hypothyroidism. Despite thyroid hormone optimization, weakness persisted, and a progressive erythematous rash developed. Further evaluation revealed antinuclear antibody (ANA) positivity at 1:320, positive anti-Mi-2α/β, and markedly elevated anti-NXP2 antibodies, with negative anti-SRP and anti-HMGCR antibodies. Muscle biopsy demonstrated prominent myofiber necrosis with sparse inflammatory infiltrates, confirming NDM. High-dose corticosteroids and methotrexate resulted in gradual clinical improvement. Given the anti-NXP2 positivity, comprehensive malignancy screening was initiated. This case highlights the diagnostic challenge of distinguishing hypothyroid myopathy from inflammatory myopathy and expands the spectrum of anti-NXP2-associated disease to include SRP-negative necrotizing phenotypes. Persistent weakness or elevated CK levels despite thyroid correction should prompt evaluation for inflammatory myopathy, including myositis-specific antibodies and muscle biopsy.
Goranti et al. (Tue,) studied this question.