Myopathies

Practice Essentials

A myopathy is a muscle disease unrelated to any disorder of innervation or neuromuscular junction. These conditions have widely varying etiologies, including congenital or inherited, idiopathic, infectious, metabolic, inflammatory, endocrine, and drug-induced or toxic.

History

Important information to obtain during the patient’s history includes the following:

• Family history: Any periodic paralysis or muscular dystrophy?
• Personal history: Presence of autoimmune disease, endocrinopathy, renal insufficiency, and/or alcoholism? Previous episodes of severe weakness (eg, postexercise, after exposure to cold [possibly one of periodic paralyses]; post high-carbohydrate meals [familial hypokalemic periodic paralysis])
• Medications (eg, steroids, lipid-lowering agents, retroviral agents, alcohol, colchicine, pentachlorophenol [PCP], heroin)
• Occupational and travel history (potential ingestion of barium chloride or carbonate [acute hypokalemic paralysis])

Signs and symptoms

The common symptoms of myopathy are muscle weakness, impaired function in activities of daily life, and, rarely, muscle pain and tenderness. Significant muscle pain and tenderness without weakness should prompt consideration of other causes.

General signs and symptoms of myopathy include the following:

• Symmetric proximal muscle weakness
• Malaise, fatigue
• Dark-colored urine (suggests myoglobinuria) and/or fever
• Absence of sensory complaints or paresthesias; however, deep tendon reflexes (DTRs) may be diminished/absent in hypokalemic paralysis
• Very late findings: Atrophy and hyporeflexia (early presence usually implicates neuropathies)
• Normal level of consciousness
• Gottron papules in dermatomyositis: Pink-to-violaceous scaly areas over knuckles, elbows, and knees

The acuity of symptom onset may aid in the diagnosis, as follows:

• Weakness progressing over hours: Possible toxic etiology or one of episodic paralyses
• Weakness developing over days: May be an acute dermatomyositis or rhabdomyolysis
• Symptom development over a period of weeks: May be polymyositis, steroid myopathy, or myopathy resulting from endocrine causes (eg, hyperthyroidism, hypothyroidism)

Indications of which muscle groups are involved include the following symptoms:

• Proximal muscle weakness: Difficulty rising from chairs, getting out of the bathtub, climbing stairs, and/or shaving or combing the hair
• Weakness of distal muscles: Weak grasp, handwriting problems, and walking difficulties, (eg, flapping gait)

See Clinical Presentation for more detail.

Diagnosis

Laboratory testing

The following laboratory tests may be used to evaluate patients with myopathies:

• Creatine kinase (CK) levels with isoenzymes
• Levels of electrolytes, calcium, and magnesium
• Serum myoglobin levels
• Serum creatinine and blood urea nitrogen levels
• Urinalysis: Myoglobinuria indicated by positive urinalysis with few red blood cells on microscopic evaluation
• Complete blood count
• Erythrocyte sedimentation rate
• Thyroid function tests
• Aspartate aminotransferase levels

Other studies may include the following:

• Electrocardiography
• Antinuclear antibody levels
• Genetic testing
• Electromyography
• Magnetic resonance imaging (to assess complications or rule out neurologic disease)
• Muscle biopsy

See Workup for more detail.

Management

The treatment of a myopathy is dependent on its etiology and can range from supportive and symptomatic management to therapy for specific conditions. Such treatments may include the following:

• Supportive: Management of airway, breathing, circulation; hydration; intensive care management may be needed in some cases
• Drug therapy
• Physical therapy
• Bracing
• Surgery

See Treatment for more detail.

• References

Background

Myopathy is a muscle disease unrelated to any disorder of innervation or neuromuscular junction. Etiologies vary widely. The common symptoms are muscle weakness, impaired function in activities of daily life, and, rarely, muscle pain and tenderness. Presence of discolored or dark urine suggests myoglobinuria.

For the emergency physician, it is important to distinguish neurologic from muscular dysfunction. However, in the face of profound weakness, establishing ABCs (airway, breathing, circulation) with attention to airway and aspiration precautions and providing supportive care are indicated while inpatient consultation and detailed studies are performed.

• References

Pathophysiology

Most congenital myopathies or inherited myopathies are chronic slowly progressive diseases. The emergency physician rarely attends to a patient specifically to treat congenital myopathy unless acute deterioration occurs. Emergency physicians attend to patients with metabolic,^[1] inflammatory, endocrine, and toxic causes of myopathy more often than those with congenital causes because of the acute or subacute onset of symptoms associated with noncongenital forms.^[2]

Periodic paralyses are a group of diseases that cause patients to present with acute weakness due to potassium shifts, leading to muscle dysfunction. A genetic defect of the sodium ion channel in muscle cell membranes is responsible for the paralysis, which may last from hours to days.

• References

Etiology

Idiopathic myopathies are thought to result from immune-mediated phenomena including sarcoidosis with myopathy, polymyositis, and dermatomyositis. Some idiopathic myopathies are associated with connective tissue disease, eg, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and polyarteritis nodosa.

Acute alcoholic myopathy should be considered in patients who, after binging on alcohol, present with muscle pain that mostly involves limb weakness and myoglobinuria. Note the following:

• Significance of acute alcoholic myopathy is that the precipitation of myoglobin in the renal tubules can cause acute renal tubular necrosis
• Aggressive hydration and, occasionally, administration of mannitol and furosemide to increase diuresis, are essential to maintain renal function
• Alcohol, in addition to the acute syndrome of muscle necrosis, causes a more chronic myopathy associated with gradual progressive weakness and atrophy that usually involves the hip and shoulder girdle; this chronic myopathy does not result in myoglobinuria or elevated creatine kinase-MM (CK-MM) levels

Infectious causes include the following:

• Trichinosis
• Cysticercosis (Taenia solium)
• Toxoplasmosis
• Human immunodeficiency virus (HIV)^[3]
• Coxsackie A and B viruses
• Influenza
• Lyme disease
• Staphylococcus aureus muscle infection (frequent cause of pyomyositis)

Endocrine causes of myopathy include the following:

• Addison disease, particularly when fluid and electrolyte problems are present
• Cushing disease
• Hypothyroidism (CK may be mildly elevated)
• Hyperthyroidism (CK may be normal)
• Hyperparathyroidism

Drug-induced or toxic causes of myopathy include use of the following^[4] :

• Steroids (especially with prolonged high doses, divided doses over 25 mg/day, fluorinated steroid use)
• Zidovudine (AZT)
• Lovastatin and other statins^{[5, 6]}
• Cocaine
• Colchicine
• Amiodarone and other agents that inhibit CYP3A4 when combined with simvastatin

Acute periodic paralysis may be classified as hypokalemic, hyperkalemic, or normokalemic. Note the following:

• Normokalemic paralysis causes the most severe and prolonged attacks
• Patients usually feel well between attacks, but some have myotonia (ie, muscle stiffness) or residual weakness after repeated episodes
• A genetic defect has been linked to these diseases, but in some instances, hypokalemia may cause acute weakness in healthy individuals
• Acute hypokalemic periodic paralysis may be primary (ie, familial) or secondary to excessive renal or GI losses or endocrinopathy; in these cases, intracellular shift of potassium depolarizes the cell membrane, rendering it inexcitable and ensuring that no muscle contraction can occur, with the result that the patient experiences paralysis; this may occur independent of the sodium-potassium pump
• Familial periodic paralysis usually occurs in Caucasian males, is autosomal dominant, and may last as long as 36 hours
• Attacks usually occur at night or in early morning upon awakening and can be precipitated by a diet high in carbohydrates, rest following exercise, or glucose and insulin given intravenously

Thyrotoxic periodic paralysis and Conn syndrome (ie, primary hyperaldosteronism) occur in Asians and are considered to have low potassium as the mechanism for paralysis. Treatment of the underlying disease and electrolyte disorder are curative.

Excessive licorice ingestion, as well as a myriad of other causes of hypokalemia, can cause paralysis.

Muscular dystrophies are chronic, progressive, inherited myopathies that present from early childhood to adolescence, as follows:

• Duchenne muscular dystrophy (DMD), observed in boys younger than 5 years, causes the most severe disease; cardiomyopathy is common in affected children
• Weakness and muscle wasting in a child with elevated CK occurs with DMD, but other dystrophies (eg, fascioscapulohumeral, limb-girdle, myotonic) may occur in boys and girls with normal muscle-enzyme levels
• Patients with mild cases may lead fairly normal lives, but progressive weakness and scoliosis impairing pulmonary function often results in recurrent infections and exacerbation of weakness

• References

Prognosis

The prognosis varies depending on the etiology. The morbidity and mortality of myopathies is related to the etiology of the condition, severity of disease, and the presence of comorbid conditions. Severe weakness may lead to respiratory failure and death.

Thyrotoxic hypokalemic periodic paralysis is known to occur in Asian men, and one study suggests that Polynesians are also at risk for this condition.^[7]

• References

History

Obtain the family history to determine presence of periodic paralysis or muscular dystrophy. Personal history of autoimmune disease, endocrinopathy, renal insufficiency, and/or alcoholism should be noted.

Discuss any previous episodes of severe weakness, particularly any that occurred after exercise or exposure to cold temperatures, which may indicate one of the periodic paralyses. Some patients with familial hypokalemic periodic paralysis may note that the symptoms occur after eating high-carbohydrate meals.

History of medication use is very important. Steroids, lipid-lowering agents,^[8] retroviral agents, alcohol, colchicine, pentachlorophenol (PCP), heroin, and a myriad of other medications may cause myopathies. In some cases, the combination of multiple myopathic agents is responsible for the acute deterioration.^[9]

Occupational and travel history may lead a physician to consider ingestion of barium chloride or carbonate as a cause for acute hypokalemic paralysis. Note the following:

• These are absorbable salts (in contrast to nonabsorbable, safe, widely used barium sulfate) that may contaminate table salt or flour; absorbable salts may be used industrially for glazing pottery
• Paralysis results when passive efflux of potassium is blocked at the cell membrane and elevated intracellular potassium decreases the resting membrane potential

Symptoms noted generally include the following:

• Symmetric proximal muscle weakness
• Malaise
• Fatigue
• Patient may note dark-colored urine, fever, or both.
• No sensory complaints or paresthesias are noted with myopathies
• Atrophy and hyporeflexia are very late findings in most patients with myopathy; the early presence of these findings usually implicates neuropathies

Significant muscle pain and tenderness without weakness should prompt physicians to consider other causes.

Acuity of symptom onset aids in diagnosis, as follows:

• Weakness progressing over hours suggests a toxic etiology or one of episodic paralyses
• Weakness developing over days suggests acute dermatomyositis or rhabdomyolysis
• Symptom development over a period of weeks suggests polymyositis, steroid myopathy, or myopathy resulting from endocrine causes (eg, hyperthyroidism, hypothyroidism)

Symptoms of the patient indicate which muscle groups are involved, as follows:

• Difficulty rising from chairs, getting out of the bathtub, climbing stairs, and/or shaving or combing the hair suggests proximal muscle weakness
• Weakness of distal muscles will present with symptoms of weak grasp, handwriting problems, and walking difficulties, (eg, flapping gait)

• References

Physical Examination

Objective weakness, usually in a symmetric distribution of proximal muscle groups is observed. Muscle tenderness is rare; muscle mass should be normal. Atrophy is a very late sign with muscle disorders. Deep tendon reflexes (DTRs) and sensory perception should be normal. DTRs may be diminished or absent in hypokalemic paralysis.

Fever may occur, particularly with pyomyositis or polymyositis. Normal level of consciousness should be preserved.

Skin examination may reveal Gottron papules, which are pink-to-violaceous scaly areas over knuckles, elbows, and knees in dermatomyositis.

• References

Complications

Complications of myopathy include the following:

• Cardiac arrhythmias
• Hypertension
• Dysphagia
• Acute gastric dilation
• Respiratory failure
• Endocrinopathies
• Cataracts
• Sensorineural hearing loss
• Seizures and cerebral dysplasias
• Early death

• References

Laboratory Studies

The following laboratory tests may be used to evaluate patients with myopathies:

• Creatine kinase (CK) with isoenzymes
• Electrolytes (calcium, magnesium)
• Serum myoglobin
• Serum creatinine and blood urea nitrogen (BUN)
• Urinalysis - Myoglobinuria is indicated by positive urinalysis with few red blood cells (RBCs) on microscopic evaluation.
• Complete blood count (CBC)
• Erythrocyte sedimentation rate (ESR)
• Thyroid function tests
• Aspartate aminotransferase (AST)

• References

Other Tests

Electrocardiography

Electrocardiographic (ECG) findings suggestive of hypokalemia include the following:

• Diffuse nonspecific ST-T wave changes
• Increased PR interval
• U waves
• Wide QRS

Other studies

Steroid therapy should be withheld until a definitive diagnosis is made, but many tests that are essential for distinguishing among the varied causes of myopathy are out of the scope of the emergency physician. These tests include the following:

• Genetic testing
• Antinuclear antibody (ANA)^{[10, 11]}
• Magnetic resonance imaging (MRI)^[10]
• Electromyography (EMG)
• Muscle biopsy^{[10, 12]}

• References

Emergency Department Care

Respiratory insufficiency, associated cardiomyopathy, heart block, and aspiration may result from severe myopathy. Management is supportive.

Patients with rhabdomyolysis warrant inpatient and critical care admission to manage potentially life-threatening renal complications and hyperkalemia.

In patients with hypokalemic periodic paralysis, IV or oral potassium replacement may be indicated. Note the following:

• Swallowing usually is not impaired, and oral supplementation may blunt the acute attack
• IV potassium should be given cautiously, if used at all
• Attacks will resolve spontaneously within 4-24 hours, and hyperkalemia may result if potassium supplementation has been excessive
• Spironolactone and acetazolamide are useful for prophylaxis of attacks

In patients with hyperkalemic periodic paralysis, attacks are often so brief that no therapy is needed. Note the following:

• Some patients find that carbohydrate loading at the onset of symptoms may lessen the attack
• Glucose and insulin may be useful in lowering serum potassium levels. Kayexalate has not been shown to be effective

• References

Consultations

Consultation with one or more of the following services may be useful:

• Neurology
• Rheumatology
• Infectious disease

• References