Abstract Introduction Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterized by severe proximal muscle weakness, markedly elevated creatine kinase (CK) and myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy. IMNM is classified into three subtypes of varying clinical severity: anti-signal recognition particle (SRP), anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and seronegative immune-mediated necrotizing myopathy (SIMNM). Evidence-based treatment strategies remain limited, however, favorable responses to combination immunotherapy (corticosteroids, IVIG and other immunosuppressants) have been reported. Presented is a rare case of severe SIMNM, highlighting its diagnostic and therapeutic challenges. Case Summary A 72 year old male with extensive cardiac history, peripheral vascular disease, hyperlipidemia reportedly on dual statin therapy, prior cerebrovascular accident with residual R-sided weakness presented with progressive bilateral lower extremity weakness over several weeks leading to bedbound status, associated with bladder dysfunction, constipation, and a pruritic leg rash. Examination revealed profound ascending weakness with areflexia and markedly elevated CK (40,000 U/L). MRI of the spine showed no cord compression or demyelinating lesions, while MRI of the thighs demonstrated diffuse muscle edema and fatty atrophy. Rheumatologic and myositis antibody panels, including anti-HMG-CoA reductase and anti-SRP, were negative. Quadriceps biopsy confirmed immune-mediated necrotizing myopathy. Despite IVIG and pulse-dose corticosteroids, he developed worsening respiratory muscle weakness, hypoxic respiratory failure, and a cardiac arrest necessitating mechanical ventilation and vasopressors. Given poor neurologic recovery and persistent metabolic encephalopathy, care was transitioned to comfort measures, and the patient passed away in hospice. Discussion SIMNM is a rare and diagnostically challenging subset of autoimmune myopathies, often lacking myositis-specific antibodies that guide management. Our differential diagnosis initially included statin-induced necrotizing myopathy, dermatomyositis given proximal muscle weakness and lower extremity rash, and Guillain-Barré syndrome given the ascending weakness, areflexia, and respiratory compromise. However, the absence of HMGCR antibodies and biopsy findings of myofiber necrosis with minimal inflammation supported our diagnosis of SIMNM. This case highlights the diagnostic challenge posed by antibody-negative presentations and the critical role of biopsy in establishing diagnosis. Additionally, early ICU monitoring was instrumental given severe diaphragmatic involvement manifested by hypoxic respiratory failure. Nonetheless, the patient subsequently experienced cardiac arrest necessitating mechanical ventilation and use of vasopressors. Conclusion This case underscores the diagnostic complexity and therapeutic challenges of SIMNM, emphasizing that delay and treatment can lead to rapid, catastrophic deterioration, making early biopsy, aggressive immunotherapy, and close interdisciplinary collaboration are critical to mitigating respiratory compromise and improving outcomes This abstract is funded by: none
Henry et al. (Fri,) studied this question.
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