What is the diagnosis and treatment for myopathy (muscle disease)?

From the Guidelines

Myopathy is a disease of the skeletal muscles that causes weakness and dysfunction, and its management should prioritize reducing morbidity and mortality, and improving quality of life, through early diagnosis and intervention with treatments such as corticosteroids, immunosuppressants, and physical therapy, as supported by the most recent and highest quality study 1.

Diagnosis and Treatment

Myopathy can be inherited genetically or acquired through various causes including autoimmune disorders, medications, infections, or metabolic disturbances. Common symptoms include muscle weakness (typically in the proximal muscles closer to the trunk), fatigue, muscle pain, and sometimes muscle wasting. Diagnosis typically involves:

• Blood tests for muscle enzymes like creatine kinase (CK) 1
• Electromyography (EMG) 1
• Muscle biopsy 1
• Sometimes genetic testing 1 Treatment depends on the underlying cause, with options including:
• Inflammatory myopathies: corticosteroids (prednisone 0.5-1 mg/kg/day) or immunosuppressants like methotrexate (15-25 mg weekly) or azathioprine (1-3 mg/kg/day) 1
• Toxic myopathies: discontinuation of the offending medication
• Metabolic myopathies: specific dietary modifications or enzyme replacements
• Physical therapy to maintain muscle strength and function, regardless of cause 1

Prognosis and Outcome

The prognosis varies widely depending on the specific type of myopathy, with some being progressive and others responding well to treatment. Early diagnosis and intervention generally lead to better outcomes by preventing irreversible muscle damage and maintaining quality of life 1. Some key points to consider in the management of myopathy include:

• The importance of a multidisciplinary approach to treatment, involving specialists such as rheumatologists, neurologists, and physical therapists 1
• The use of novel biomarkers, such as interleukin 6 and type 1 interferon-regulated genes, to monitor disease activity 1
• The potential benefits of magnetic resonance imaging (MRI) in assessing muscle inflammation and guiding treatment decisions 1

From the FDA Drug Label

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years

Myopathy is a potential side effect of high-dose corticosteroid therapy, particularly in patients with neuromuscular transmission disorders or those receiving neuromuscular blocking drugs. Key characteristics of this condition include:

• Generalized muscle weakness
• Involvement of ocular and respiratory muscles
• Potential for quadriparesis
• Elevation of creatinine kinase
• Prolonged recovery time (weeks to years) after stopping corticosteroids 2

From the Research

Definition and Causes of Myopathy

• Myopathy refers to a group of muscle disorders that can be caused by a variety of factors, including drugs, alcohol, thyroid disease, osteomalacia, idiopathic inflammatory myopathies (IIM), hereditary myopathies, malignancy, infections, and sarcoidosis 3.
• Metabolic myopathies are disorders that affect skeletal muscle substrate oxidation, and can be caused by impairments in glycogenolysis/glycolysis, fatty acid transport/oxidation, and mitochondrial metabolism 4.

Diagnostic Approach

• The diagnostic approach to myopathy should include a clinical assessment to distinguish proximal myopathy from other conditions, identify patients who need prompt attention, and determine the underlying cause of myopathy 3.
• Initial evaluation should include simple tests such as creatine kinase, thyroid function, and (25)OH vitamin D levels, while further evaluation including neurophysiological studies, muscle imaging, and muscle biopsy should be considered for patients with no toxic, metabolic, or endocrine cause found 3.
• Exercise stress testing, blood tests (e.g. creatine kinase, acylcarnitine profile, lactate, amino acids), urine tests (e.g. organic acids, myoglobin), muscle biopsy, and targeted or untargeted genetic tests may be necessary to evaluate metabolic myopathies 4.
• A diagnostic algorithm can be used to facilitate a more efficient work-up in patients with myalgia, exercise intolerance, or fatigue, and can help determine which combination of ancillary investigations should be employed in different subgroups 5.

Diagnostic Yield and Clinical Utility

• Open muscle biopsy can be a useful diagnostic tool in suspected myopathy, with a specific clinical diagnosis made in 43% of cases, and treatment changed in 33% of cases 6.
• The diagnostic yield of muscle biopsy can be predicted by pre-biopsy factors such as positive family history of myopathy and findings of myopathic irritability on electromyography 6.
• A combination of ancillary investigations, including CK levels, EMG, ultrasound, and muscle biopsy, can contribute to predicting a myopathy, with positive predictive values ranging from 0.32 to 0.78 5.

Management

• Management of myopathy depends on the underlying cause, and may include removal of offending agents, correction of endocrine or metabolic problems, corticosteroids and immunosuppressive therapy for IIM, and physical therapy, rehabilitation, and genetic counseling for muscular dystrophies 3.
• Lifestyle, exercise, and nutritional modifications, as well as cofactor treatments and avoidance of specific triggers, may be necessary for patients with metabolic myopathies 4.