Case Presentation: A 38 year old woman with a history of alcohol use disorder was admitted with a month of gradually progressive weakness of the legs. She then developed shoulder girdle weakness, and eventually weakness, tingling, and numbness of the hands and feet. The day prior to her presentation, she developed dysarthria, shortness of breath, and occasional chills.On evaluation in the emergency, she was found to be hypoxic, hypotensive, and tachycardic to 140 bpm. Labs were significant for CK 19,455 U/L, troponin 1282.6 pg/ml, aldolase 41 U/L, NT-pro brain natriuretic peptide 627 pg/ml. She was intubated due to impending respiratory failure and experienced a brief cardiac arrest with down time 2 minutes. Lumbar puncture revealed protein 55 mg/dl and WBC 1/mcL. Initial echocardiogram revealed reduced systolic function with septal hypokinesis. Subsequent minimally invasive hemodynamic monitoring (FloTrac) revealed low cardiac output and index refractory to norepinephrine and epinephrine infusions, necessitating milrinone infusion. Steroid pulse of methylprednisolone 1g/day for 3 days was initiated and an autoimmune panel was sent. ANA resulted as 1:80, anti-SSA 1.2 IU/ml, however the rest of the panel including anti-HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) and anti-SRP (signal recognition peptide) was negative. She was initiated on mycophenolate mofetil 1500 mg twice daily and a prednisone taper. MRI of her thighs showed diffuse edema consistent with myositis. Quadriceps muscle biopsy eventually resulted as necrotizing myopathy with positive MHC Class 1 immunohistochemistry (IHC), and a diagnosis of antibody-negative immune mediated necrotizing myopathy (IMNM) was established. As cardiac function gradually improved, she was weaned off milrinone and pressors, and extubated. Muscle strength improved, and she is currently ambulatory but continues to have foot drop.
Discussion: IMNM is a rare, relatively recently described subset of idiopathic inflammatory myopathy (IIM), characterized by progressive symmetrical proximal limb weakness, and a variety of extramuscular manifestations. Diagnostic histological features are prominent necrosis and regeneration of muscle fibers with a relative lack of lymphocytic infiltrate. Autoimmune etiology is determined by IHC positivity for MHC Class 1 or membrane attack complex. Till date, two autoantibodies have been noted in IMNM patients: anti-HMGCR and anti-SRP. Extra-muscular manifestations of IMNM include rash, arthritis, myocarditis, and interstitial lung disease. Notably, myocarditis presenting with chest pain, arrhythmias, and congestive heart failure have been noted in upto 40% patients with anti-SRP IMNM. However, overt clinical cardiac involvement has been rarely reported in anti-HMGCR or antibody-negative IMNM, though subclinical arrhythmias and echocardiographic changes have been noted.
Conclusions: The pathogenesis and manifestations of IMNM are subjects of active research, with much left to be uncovered. Our case of antibody-negative IMNM is to our knowledge the only one reported till date to present with cardiogenic shock requiring inotropes, and resolving with immunosuppressive therapy. We hope this will be a useful addition to the expanding literature regarding this novel field.
