Case Presentation: A 56-year-old male with end-stage renal disease on hemodialysis, hypertension, dyslipidemia (on atorvastatin), diabetes, and prior cerebrovascular accident without residual deficits presented with two months of progressive weakness, dysphagia, and polyarthralgia. The weakness led to recurrent falls and impaired mobility. Symptoms began in his left leg and gradually progressed to the right leg, bilateral arms, and trunk. On exam, he had marked bilateral weakness (1/5 hip extension, 2/5 knee flexion/extension) and tenderness to light palpation in his bilateral thighs and calves. There was mild weakness in shoulder abduction/flexion/extension (right 4/5, left 3/5). There were no cutaneous findings. Laboratory studies revealed creatine kinase (CK 61,334 U/L), erythrocyte sedimentation rate >130 mm/hr, C-reactive protein 179 mg/L, and an antinuclear antibody titer of 1:80. Magnetic resonance imaging (MRI) of the bilateral thighs showed diffuse edema most pronounced in the right musculature. Brain MRI showed chronic lacunar infarct but no acute pathology. Cervical spine MRI revealed severe C3-C5 stenosis and C5 myelomalacia. Differential diagnosis favored either autoimmune myositis or, less likely, drug-induced direct muscle toxicity. Atorvastatin was discontinued. An extended myositis panel, including Anti-HMGCR and AntiSRP, was negative. Given minimal changes in exam and CK and strong concern for autoimmune myositis, empiric treatment with pulse-dose corticosteroids and intravenous immunoglobulin (IVIG) was initiated, with resultant rapid decline in CK levels. Biopsy of the right vastus lateralis showed findings consistent with autoimmune necrotizing myositis. Evaluation for occult malignancy was unremarkable. He was diagnosed with seronegative immune mediated necrotizing myositis (IMNM). Strength and CK improved with glucocorticoid taper and monthly IVIG. He was ultimately discharged on IVIG monotherapy with planned outpatient follow-up.
Discussion: Immune mediated necrotizing myositis (IMNM) is characterized by subacute progressive symmetrical proximal muscle weakness with marked CK elevation. It may also include dysphagia, neck muscle weakness, and respiratory compromise. It is thought to be an acquired autoimmune condition, triggered by environmental factors, such as viral infections or statin exposure, in genetically predisposed individuals. Most patients with IMNM have positive SRP or HMGCR antibodies; however, up to 40% of patients may be “seronegative”. These patients require biopsy for diagnosis. Histopathology typically reveals necrotic fibers with minimal lymphocytic infiltration. While challenging, accurate diagnosis of seronegative IMNM remains crucial. Prompt treatment, with corticosteroids and/or IVIG can significantly improve outcomes and reduce long-term disability. Additionally, seronegative IMNM has been associated with higher rates of malignancy and cardiac involvement, underscoring the importance of screening and close follow-up.
Conclusions: In cases of suspected inflammatory myopathy with negative serology, hospitalists should maintain a low threshold for muscle biopsy. Timely diagnosis of immune mediated necrotizing myositis enables early aggressive treatment, improves functional outcomes, and facilitates appropriate risk stratification for associated malignancy and cardiac complications.