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.

Autoimmune necrotizing myositis. Presentation of a clinical case

Inflammatory myopathies (IM) or myositis are a heterogeneous group of muscle diseases of rare occurrence. Such diseases are characterized by inflammation of the different components of muscle tissue, which can occur either in isolation or, more commonly, as part of a systemic disorder. Immune-mediated necrotizing myopathies (IMNM) are a type of autoimmune myopathy characterized by proximal muscle weakness, myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy and infrequent extramuscular involvement. Even though there are clinical and histopathological similarities. The spectrum of inflammatory myopathies is considerably variable. Therefore, the performance of complementary studies is essential for the proper identification of the IM subtype to contribute accurately on treatment so determine the better prognosis). The present article shows the case of a young 29 years old, with no personal and family history background of autoimmune disease and no relevant pathological back-ground. The patient consulted the medical ward of the Institution with pain, functional impairment of upper and lower extremities, muscle weakness mainly located in the pectoral girdle area and, although to a lesser degree, in the pelvic girdle area. It was also associated with asthenia, tendency to drowsiness and hyporeactivity.

Updates in Diagnosis and Managements of Polymyositis: Simple Review

Idiopathic inflammatory myopathies (IIMs) includes an unusual group of acute, chronic, and subacute developed diseases of skeletal muscle characterized by moderate to severe muscle weakness and inflammation.Polymyositis is generally considered to be a prototypic T cell-mediated autoimmune myopathy, while DM was traditionally associated with a humoral-driven microangiopathy, though the putative autoantibodies and their targets have yet to be identified, and there is increasing evidence implicating the type I interferon pathway in the pathogenesis of the disease. Women between the ages of 50 and 70 are the most typically affected. Proximal muscular weakness is the most common clinical symptom. Inflammatory arthritis, Raynaud's phenomenon, myocarditis, and interstitial lung disease are all examples of extramuscular involvement. In this review, we overview updates in diagnosis and managements of polymyositis.

Muscle shear wave elastography, conventional B mode and power doppler ultrasonography in healthy adults and patients with autoimmune inflammatory myopathies: a pilot cross-sectional study

Background Before the role of shear wave elastography (SWE) and B mode ultrasound (US) in the diagnosis of different forms of idiopathic inflammatory myopathies (IIM) can be investigated, normative data is required. This study aimed to describe and then compare normative SWE and B mode ultrasound metrics of muscles in healthy controls and patients with IIM. Methods Twenty nine healthy adult controls and 10 IIM patients (5 with inclusion body myositis and 5 with necrotising autoimmune myopathy) underwent a full clinical examination, laboratory investigations, SWE and US measurements of selected proximal and distal limb muscles. Shear wave speed (SWS) and multiple US domains [echogenicity, fascial thickness, muscle bulk and power Doppler (PD)] were measured in both groups. Results In healthy controls (n = 29; mean age 46.60 ± 16.10; 44.8 % female), age was inversely correlated with SWS at the deltoid (stretch) (Rs. -0.40, p = 0.030) and PD score at the deltoid (rest) (Rs. -0.40, P = 0.032). Those ≥ 50 years old had a lower SWS at the deltoid (stretch) compared to the < 50 year group (2.92 m/s vs. 2.40 m/s, P = 0.032). Age correlated with increased echogenicity in the flexor digitorum profundus (Rs. 0.38, P = 0.045). Females had a smaller muscle bulk in the deltoid (P = 0.022). Body mass index (BMI) was inversely associated with SWS in the deltoid (stretch) (Rs – 0.45, P = 0.026), and positively correlated with echogenicity in the deltoid (Rs. 0.69, P = 0.026). In patients ≥50 years of age, patients with IIM (mean age 61.00 ± 8.18; females 20.0 %) had a higher proportion of abnormal echogenicity scores at the flexor digitorum profundus (FDP) (40.00 % vs. 14.30 %, P = 0.022) and tibialis anterior (TA) (80.00 % vs. 28.60 %, P = 0.004). Fascial thickness was lower in the FDP (0.63mm vs. 0.50mm, p = 0.012) and TA (0.58mm vs. 0.45mm, P = 0.001). Conclusions Our findings suggest there is scope for US techniques to be useful for diagnostic screening of affected muscles in patients with IIM, especially in those with suspected inclusion body myositis or necrotising autoimmune myopathy. We provide normative data for future studies into SWE and US techniques in skeletal muscle. The differences between IIM patients and controls warrant further study in a broader IIM patient cohort.

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).

Vaccination as a possible trigger for immune-mediated necrotising myopathy

Immune-mediated necrotising myopathy is a rare autoimmune myopathy characterised by severe progressive muscle weakness, elevated levels of creatine kinase (CK), and necrosis with minimal inflammatory cell infiltration on muscle biopsy. We report a case of a previously healthy 42-year-old woman who presented with progressive muscle weakness 2 weeks after immunisation for yellow fever, tetanus/diphtheria and hepatitis B. Her symptoms started from the lower limbs and progressed to the upper limbs and cervical region associated with dysphagia, making her wheelchair bound. Electromyography showed a myopathic pattern, with a CK level of 12.177 U/L (reference value: 26–190 U/L), and biceps brachial muscle biopsy confirmed necrosis and regeneration fibres. The immunoblot test was positive for antisignal recognition particle. She was successfully treated with prednisone (1 mg/kg/day). Although considered safe, vaccines may cause allergic reactions or trigger autoimmune disorders. Currently, a causal relationship between them cannot be established.

Statin-induced necrotising autoimmune myopathy: a rare complication of statin therapy

Statin-induced necrotising autoimmune myopathy (SINAM), a rare complication of statin use, presents with significant proximal muscle weakness and raised creatine kinase (CK) levels (50–100 times). This is different from other musculoskeletal conditions caused by statin use. Anti-hydroxy-methyl-glutaryl-coenzyme A reductase (HMG-CoA) reductase antibody is usually positive in SINAM and it generally indicates good response to immunosuppressive medications. We report a case of a 52-year-old man who presented with a 2-month history of significant upper and lower extremity proximal muscle weakness and a CK level of >10 000. He was started on atorvastatin for myocardial infarction 3 years ago. MRI pelvis, including proximal thigh, showed diffuse muscle oedema to all muscle groups. Muscle biopsy was suggestive of necrotising myopathy. His HMG-CoA reductase antibody was also positive. His treatment regimen consisted of immunosuppressants, including steroids. He also required extensive physiotherapy and showed response to treatment when reviewed in the outpatient clinic 9 months later.