Muscle disease can be caused by:

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  Inflammatory diseases: polymyositis, dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy

  
  
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  Medications: most commonly statins and corticosteroids, but other immunosuppressive agents in addition to steroids (e.g., cyclosporine, tacrolimus), zidovudine, and amiodarone can also cause myopathy

  
  
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  Systemic diseases: HIV, endocrine disease, rheumatologic disease, critical illness

  
  
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  Genetic disorders, which can be further divided into genetic defects in:

  
  
  
  
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    Structural muscle proteins: muscular dystrophies, congenital myopathies

    
    
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    Metabolic pathways: glycogen storage diseases, disorders of lipid metabolism

    
    
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    Mitochondria: mitochondrial myopathies such as myoclonic epilepsy with ragged red fibers (MERRF)

    
    
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    Ion channels: periodic paralyses

The hallmark of muscle disease is weakness. Diseases of muscle are distinguished from central nervous system or peripheral nervous system causes of weakness by lack of upper or lower motor neuron signs (although severe weakness can cause decreased reflexes), lack of sensory changes, and by the pattern and distribution of weakness. The most common pattern of weakness in diseases of muscle is symmetric proximal weakness, although there are myopathies that specifically affect particular distal muscle groups in isolation (e.g., distal myopathies) or in addition to proximal muscles (e.g., inclusion body myositis), and some muscle diseases can begin (and/or remain) asymmetric (e.g., inclusion body myositis, fascioscapulohumeral muscular dystrophy). Weakness in some muscle diseases develops insidiously (e.g., dermatomyositis, polymyositis, muscular dystrophies), but in others it can be rapidly progressive (e.g., immune-mediated necrotizing myopathy). In some muscle diseases weakness occurs only with particular precipitants (e.g., exercise in metabolic myopathies, potassium level in periodic paralyses). When weakness is exercise–induced, diseases of the neuromuscular junction must also be considered (see Ch. 29).

An elevated serum creatine kinase (CK) is seen in many muscle diseases, but may not necessarily be elevated in all muscle diseases. CK elevation can also be caused by muscle injury, exercise, and generalized tonic-clonic seizures. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (“liver enzymes”) do not just rise in liver disease, but may also be elevated due to muscle breakdown. Aldolase elevation can also be caused by either liver or muscle disease. An increase in gamma-glutamyl transferase (GGT) with elevated AST/ALT can help to distinguish liver injury as the cause of the rise in AST/ALT because GGT is present only in liver and not in muscle. Myoglobinuria suggests muscle breakdown, which can occur due to primary muscle disease or in the setting of muscle injury (e.g., extreme exercise, toxins, trauma).

In nerve conduction studies in muscle diseases, compound motor action potential (CMAP) amplitudes may be reduced due to loss of muscle fibers, but sensory nerve action potentials (SNAPs) and conduction velocities should be normal (unless there is concurrent neuropathy). Electromyography (EMG) in muscle diseases can reveal increased insertional activity, fibrillation potentials, decreased motor unit action potential (MUAP) amplitude and duration with polyphasia, and/or early recruitment and rapid firing rate of MUAPs (see “Electromyography” in Ch. 15). Myotonia on EMG may be seen in the myotonic dystrophies, myotonia congenita, and paramyotonia congenita.

Muscle MRI can demonstrate inflammatory changes in muscle in inflammatory myopathies. Muscle biopsy can reveal characteristic specific histologic patterns of the various myopathies, and also allows for immunostaining for particular enzymes in order to diagnose metabolic myopathies.

The inflammatory myopathies include dermatomyositis, polymyositis, inclusion body myositis, and immune-mediated necrotizing myopathy. Details of these diseases are compared in Table 30–1, and some general points are noted below.

Dermatomyositis and Polymyositis

Dermatomyositis and polymyositis have many similar features. Both cause proximal symmetric weakness of subacute to chronic onset, are more common in women, tend to present prior to age 50, may be associated with interstitial lung disease and/or cardiomyopathy, may be associated with underlying malignancy (more common with dermatomyositis), may have overlapping features with systemic autoimmune diseases, often have elevations in serum CK (although not always), and generally respond to immunomodulatory therapy. Dermatomyositis and polymyositis are distinguished from one another predominantly by the presence of skin findings in dermatomyositis and differing pathologic findings on muscle biopsy. The dermatologic features of dermatomyositis may precede, co-occur with, or follow the muscle symptoms, and can include findings on the knuckles (Gottron’s papules), neck (called the V sign due to its V shape), back (shawl sign), and eyelids (heliotrope rash).

Inclusion Body Myositis

Inclusion body myositis differs from dermatomyositis and polymyositis in several ways: It is more common in men, onset is generally after age 50, it causes distal weakness (finger flexion and foot dorsiflexion) in addition to proximal weakness (particularly in the quadriceps), it may present asymmetrically, and there is no response to immunomodulatory therapy. Dysphagia is common and facial weakness can also occur.

Immune-Mediated Necrotizing Myopathy

Immune-mediated necrotizing myopathy can occur in the context of statin use, malignancy (most commonly gastrointestinal malignancy), or associated autoimmune disease (most commonly mixed connective tissue disease or scleroderma). The course is generally more rapid in onset than the other inflammatory myopathies, and the CK is often extremely elevated. When associated with statin use, antibodies to HMG-CoA reductase may be present; in non–statin-associated cases, anti–signal recognition particle (SRP) antibodies may be present.

The muscular dystrophies are diseases caused by genetic defects in muscle proteins. They differ in the pattern of muscles affected, age of onset, associated nonmuscular features (e.g., cardiac disease), and pattern of inheritance. Diagnosis is made by targeted genetic testing based on clinical phenotype and family history. Treatment of the muscular dystrophies is largely supportive. Duchenne muscular dystrophy is the only muscular dystrophy for which a disease-modifying treatment is available (steroids). Details of the muscular dystrophies are compared in Table 30–2, and some general points are noted below.