A 53-year-old African-American woman presents to her primary care doctor with increasing difficulty climbing the stairs. She noticed the weakness approximately 3 months ago. It has gotten progressively worse since that time. She has also noticed increasing difficulty combing her hair, standing from a seated position, and experiences muscle aches. Her medical history is significant for hypertension treated with lifestyle modification and gastroesophageal reflux disease (GERD). Her temperature is 98.6°F (37.0°C), blood pressure is 130/65 mmHg, pulse is 80/min, and respirations are 16/min. She has 3/5 strength to shoulder abduction and hip flexion bilaterally. Her strength is 5/5 to wrist extension and ankle plantar flexion. No skin rashes are noted. Which of the following is the most accurate test to confirm this patient’s diagnosis?
Serum creatine kinase
Muscle biopsy
Electromyography
Serum aldolase
Muscle biopsy
This patient with insidious, subacute, progressive, symmetric proximal muscle weakness (difficulty climbing the stairs, combing her hair, standing from a seated position) without associated skin lesions most likely has polymyositis. The most accurate diagnostic test for polymyositis is muscle biopsy.

Polymyositis is caused by an autoimmune reaction that leads to cell-mediated cytotoxicity against unidentified skeletal muscle antigens, primarily affecting the endomysium. It is more often found in women, patients between 30-60 years of age, and African-Americans. Clinical features of polymyositis include symmetric proximal muscle weakness that may be accompanied by myalgia, dysphagia (due to pharyngeal muscle weakness), restrictive lung disease (due to respiratory muscle weakness), cardiac involvement (myocarditis, heart failure), interstitial lung disease, and increased risk of malignancy. There are no accepted diagnostic criteria for polymyositis; however, diagnosis is usually secured with a combination of clinical features and other tests. Routine initial studies can include a complete blood count, complete metabolic panel, C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, aldolase, creatine kinase, autoantibodies (anti-nuclear antibody, anti-Jo-1), and electromyography (EMG). Muscle biopsy of an affected muscle is the gold standard for diagnosis and will typically show muscle fiber damage, CD8+ T cells in the endomysium, and overexpression of MHC-I on the sarcolemma. First-line treatment of polymyositis includes glucocorticoids and a steroid-sparing agent (methotrexate, azathioprine). Subsequent treatments can include intravenous immunoglobulins, rituximab, or plasmapheresis.

Amato et al. review the evaluation and treatment of inflammatory myopathies such as polymyositis, dermatomyositis, and inclusion body myositis. They found that polymyositis typically presents in adult life with symmetric proximal leg greater than arm weakness. They recommend that a muscle biopsy be done on any patient considered to have polymyositis, preferably prior to starting immunosuppressive treatment.

Incorrect Answers:
Answer A: Electromyography (EMG) can help distinguish myopathic weakness (e.g., polymyositis) from neuropathic causes of weakness (e.g., amyotrophic lateral sclerosis, myasthenia gravis). Characteristic EMG findings include fibrillations, early recruitment of motor unit potentials, and abnormal low-amplitude motor unit potentials. EMG is not a confirmatory test and is less sensitive than muscle biopsy for diagnosing myositis.

Answer B: MRI can be used to demonstrate areas of edema, atrophy, fatty replacement, and calcification in patients with suspected polymyositis. MRI can assess large regions of muscle, thus avoiding sampling error with muscle biopsy. The findings in MRI are nonspecific and require correlation with muscle biopsy for definitive diagnosis. MRI can also be used to help select the site of muscle biopsy.

Answer D: Serum aldolase can occasionally be used in the diagnostic investigation of suspected polymyositis if creatine kinase is normal. Aldolase elevation is nonspecific and may be seen in fasciitis, drug-induced myositis, and connective tissue disease-associated interstitial lung disease.

Answer E: Serum creatine kinase (CK) is the most sensitive muscle enzyme exam and should be part of the initial diagnostic investigation of any patient with suspected polymyositis. CK elevation is nonspecific and may be seen in myriad conditions such as inflammatory insult, metabolic injury, drug-induced injury, and infection.

Bullet Summary:
Muscle biopsy is the gold standard for the diagnosis of polymyositis.