Rapidly Progressive Proximal Weakness

A 53-year-old woman had development of subacute-onset muscle weakness resulting in difficulty climbing stairs, rising from a chair, and reaching over her shoulders. She reported no dysphagia, dysarthria, dyspnea, or diplopia. She also disclosed no rash, joint pain, or urine discoloration. She had no history of statin exposure. There was no family history of neuromuscular disorders, early cataracts, cardiac arrhythmia, or cardiomyopathy. Two months of treatment with prednisone had resulted in no clinical improvement. Neurologic examination indicated moderate neck flexor, shoulder, and hip girdle muscle weakness, with sparing of cranial muscles. There was no action- or percussion-induced myotonia. Needle electromyography showed short-duration, low-amplitude, and complex motor unit potentials, predominantly affecting proximal muscles, associated with fibrillation potentials and myotonic discharges in proximal and axial muscles. Her creatine kinase level was increased. Biopsy of the left quadriceps showed variation in muscle fiber size, a moderate increase in internalized nuclei, fiber splitting, and scattered necrotic and regenerating fibers. There was a mild increase in perimysial fibrous and fatty connective tissue. 3-Hydroxy-3-methylglutaryl–coenzyme A reductase antibodies were strongly positive. The patient was diagnosed with hydroxy-3-methylglutaryl–coenzyme A reductase antibody–positive necrotizing autoimmune myopathy. The patient received intravenous immunoglobulin and mycophenolate mofetil while continuing prednisone. At 1-year follow-up, she had no weakness, and her creatine kinase value was normal while she continued taking prednisone, mycophenolate mofetil, and intravenous immunoglobulin. Necrotizing autoimmune myopathy, or immune-mediated necrotizing myopathy, is a subtype of immune-mediated myopathy, clinically characterized by subacute, progressive, proximal limb weakness and persistently increased creatine kinase level. Pathologically, it is characterized by myonecrosis with minimal or no inflammation. One-third of patients with necrotizing autoimmune myopathy have myalgia.

Necrotizing myopathy presenting as congestive heart failure and life-threatening ventricular arrhythmias: a case report

Background Necrotizing autoimmune myopathy is a rare subtype of idiopathic inflammatory myopathy; however, it can be associated with fatal cardiac manifestations. Case summary A 58-year-old female patient was referred for congestive heart failure with dysrhythmia. Electrocardiograms showed ventricular arrhythmias of various QRS complex morphologies and coupling intervals with beat-to-beat differences. Despite optimal medical therapy for heart failure, the patient was admitted for the progression of dyspnoea and generalized motor weakness. The burden of non-sustained ventricular tachycardia gradually increased, and ventricular fibrillation eventually occurred. In view of a differential diagnosis of an inflammatory myocardial diseases such as sarcoidosis, a cardiac biopsy was performed. However, pathologic examinations revealed only necrotic muscle fibres without granuloma. Further examinations revealed proximal dominant motor weakness, an elevated serum creatinine-phosphokinase level, myogenic potentials on needle electromyography, and biceps muscle biopsy findings that were compatible with necrotizing autoimmune myopathy. High-dose steroid therapy improved the patient’s motor weakness, including her respiratory impairment, and successfully suppressed ventricular arrhythmias. Discussion This case suggests that intensive immunosuppressive therapy with high-dose steroid could be useful in the necrotizing autoimmune myopathy manifested as congestive heart failure and life-threatening ventricular arrhythmias.

Two Cases of Statin Induced Necrotizing Autoimmune Myopathy

Case 1: Six months ago, patient 1 presented with rhabdomyolysis with a CK of 17,622 Units/L. The statin was discontinued at that time, after which the patient noted substantial improvement in muscle symptoms. Two months later the patient was readmitted for complaints related to continued rhabdomyolysis. CK was elevated at 9800 Units/L, raising suspicion for SINAM. Physical exam findings on readmission were pertinent for 4/5 strength in proximal flexion and extension of the upper extremities bilaterally and 4/5 strength in hip flexion. Pertinent lab values on readmission include increased ALT of 122 Units/L, AST of 103 Units/L, TSH of 7.4 mIU/L, HbA1c of 6.6%, and BUN of 14.5 mg/dL. Urinalysis is positive 3+ for glucose, 1+ for ketones, and 2+ for blood. Brain MRI without contrast negative for any brain malignancies or abnormalities. Case 2: Patient 2 presented with gradual proximal muscle weakness while taking a statin for the past six months. Physical exam was notable for 4/5 strength in the biceps and triceps and 3/5 deltoid strength bilaterally. There was 4/5 strength in the knee flexors and extensors with 3/5 strength in the hip flexors bilaterally. Notable lab values include CK of 10,449 Units/L, CK-MB of 492ng/mL, fasting glucose of 160 mg/dL, ALT of 229 Units/L, and HgbA1C of 7.3%. Urinalysis was positive 3+ for glucose, 1+ for ketones, and 2+ for blood. Discussion: Statin induced necrotizing autoimmune myopathy (SINAM) is a rare complication of statin therapy in which subjects develop an immune response to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). SINAM’s pathophysiology remains poorly understood. Studies have shown that statins upregulate expression of HMGCR which serve as antibody targets in SINAM (Mohassel & Mammen, 2013). The HMGCR protein is upregulated in regenerating muscle fibers thus preferentially allowing autoantibodies to bind (Mammen et al, 2011). Additionally, complement is implicated in pathogenicity of SINAM with a study showing that C3 deficient mice had less pronounced deficiency in muscle strength (Bergua et al, 2019). This is further reinforced with a muscle biopsy in another SINAM confirmed patient showed C5b-9 sarcolemmal deposits (Sharma et al, 2019). This implicates the formation of antigen-antibody-complement complexes typical of a type III hypersensitivity reaction. Additionally, genetic risk factors for autoimmunity are important to consider. There is an association of SINAM occurrence in individuals with single nucleotide polymorphism in the SLCO1B1 that regulates hepatic uptake of drugs such as statins (SEARCH, 2008). HLA- DRB1*11:01 is associated with the formation of autoantibodies in SINAM (Mammen, 2016). Recent studies show the triple induction therapy of steroids, IVIG, and a steroid sparing immunosuppressant has been very effective (Meyer et al, 2020).

COVID-19 IgG-related autoimmune inflammatory necrotizing myositis

The COVID-19 pandemic caused by the SARS-CoV-2 virus has affected millions of people around the globe. The most common presentation of COVID-19 is fever and upper and lower respiratory tract infection. Myalgia is fairly common in the prodromal phase of the viral illness which self-resolves. There is very scant literature on autoimmune myositis triggered by COVID-19 infection. We report a case of SARS-CoV-2 infection, who presented with progressive muscle weakness with rhabdomyolysis and necrotizing autoimmune myopathy on muscle biopsy. This case report imposes awareness of musculoskeletal autoimmune processes triggered by COVID-19 which requires clinical suspicion for early diagnosis and initiation of treatment.

Combined Central Retinal Vein and Cilioretinal Artery Occlusion in the Setting of Intravenous Immunoglobulin Administration

Purpose: This work reports a case of combined vascular occlusion in the setting of intravenous immunoglobulin (IVIg) administration. Methods: The authors describe a case of combined central retinal vein and cilioretinal artery that occurred in the setting of IVIg administration. Results: A 52-year-old White man presented with a unilateral subjective scotoma that began during IVIg administered for the treatment of statin-induced necrotizing autoimmune myopathy. Examination and optical coherence tomography imaging revealed a combined nonischemic central retinal vein and cilioretinal artery occlusion. Conclusions: To the authors’ review and knowledge, this is the first reported case of combined central retinal vein and cilioretinal artery occlusion occurring in the setting of IVIg administration. This rare adverse effect is an entity to be considered in patients who are treated with IVIg.

Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies

Background Necrotizing autoimmune myopathy (NAM) is pathologically characterized by myofiber necrosis and regeneration with paucity or absence of inflammatory cells in muscle biopsy. Two autoantibodies, namely anti-signal recognition particle (SRP)-antibodies and anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)-antibodies, are typically specific with NAM. Anti-SRP-positive NAM can be associated with cardiomyopathy which responds well to immunotherapy. Here we reported an anti-SRP-antibody and anti-MDA5-antibody NAM patient who developed severe cardiomyopathy after gaining significant improvement of myopathy and subsequently accepted heart transplantation. Case presentation A NAM case with both positive anti-SRP and MDA-5 antibodies who gained significant improvement of the skeletal muscle weakness with immunotherapy, but 3 years later he developed severe dilated cardiomyopathy and at last received heart transplantation. Myocardial biopsy showed disarranged and atrophic myofibers, remarkable interstitial fibrosis without inflammatory infiltrates. Immunohistochemistry analysis revealed increased polyubiquitin-binding protein p62/SQSTM1 protein expression and the positive staining of cleaved-caspase 3 in a few cardiomyocytes. After the transplantation, the patient was symptom-free on oral prednisone (10 mg/day) and tacrolimus (2 mg/day). Conclusions We described the first case of anti-SRP and anti-MAD5 positive NAM who had received heart transplantation because of cardiopathy. Though the myopathy had been clinically improved after immunotherapy, the cardiomyopathy remained progressive and lethal. The processes of dysfunctional autophagy and augmented apoptosis were putatively pathophysiological mechanisms underlying cardiac damage in anti-SRP and anti-MAD5 positive NAM.