Diagnostic Approach to Seronegative Autoimmune-Mediated Rhabdomyolysis: A Case Report

Rhabdomyolysis is a potentially life-threatening condition caused by acute skeletal muscle injury leading to myocyte destruction and release of intracellular contents. While trauma and medications are common triggers, autoimmune-mediated necrotizing myopathies are rare. Diagnostic evaluation becomes challenging in seronegative cases. We report a 51-year-old man with multiple cardiovascular comorbidities presenting with one week of progressive proximal muscle weakness, severe back pain, and dark urine. Initial labs revealed a creatine kinase (CK) of 24,700 U/L, transaminitis, and acute kidney injury. Urinalysis showed heme positivity without red blood cells, consistent with myoglobinuria. MRI of the thighs demonstrated muscle edema. Common precipitants, including trauma, exertion, infection, toxins, thyroid disease, and statin-associated antibody-mediated myopathy, were excluded by history, serology, and laboratory workup. Despite negative autoimmune panels (anti-nuclear antibody (ANA), anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody, and anti-Jo1), the clinical course and imaging supported a diagnosis of seronegative immune-mediated necrotizing myopathy. This case highlights an unusual presentation of rhabdomyolysis with associated symptoms of proximal muscle weakness and a slow improvement in CK levels despite fluids in a patient seronegative for autoimmune markers.