Myopathies

Practice Essentials

Myopathy is a muscle disease unrelated to any disorder of innervation or neuromuscular junction. This condition has widely varying etiologies, including congenital or inherited, idiopathic, infectious, metabolic, inflammatory, endocrine, and drug-induced or toxic.

Essential update: Glycine amidinotransferase expression in statin-induced myopathy

Differences in susceptibility to statin-induced myopathy may be associated with genetically determined variation in expression of the glycine amidinotransferase (GATM) gene.[1, 2] In a study of lymphoblastoid cell lines from 480 participants in a clinical trial of simvastatin, Mangravite et al identified 6 expression quantitative trait loci (QTL) that interacted with simvastatin exposure. One of these was rs9806699, a cis-expression quantitative trait locus (eQTL) for the GATM gene; GATM encodes the rate-limiting enzyme in creatine synthesis.[1, 2]

Not only was the GATM locus significantly associated with a reduction in risk for statin-induced myopathy in 2 independent populations (patients carrying the rs9806699 locus vs those who do not carry it), but the investigators also indicated that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy.[1, 2] These findings led Mangravite et al to suggest that “using a novel cell-based screen for gene-by-treatment effects on transcriptional expression”[2] for selective screening of genetic variations in patients on statins may have the potential to lower the risk of statin-induced myopathy or other adverse effects of these agents.[1, 2]

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 weaknessMalaise, fatigueDark colored urine (suggests myoglobinuria) and/or feverAbsence 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 consciousnessGottron 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 paralysesWeakness developing over days: May be an acute dermatomyositis or rhabdomyolysisSymptom 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 isoenzymeslevels of electrolytes, calcium, and magnesiumSerum myoglobin levelsSerum creatinine and blood urea nitrogen levelsUrinalysis: Myoglobinuria indicated by positive urinalysis with few red blood cells on microscopic evaluationComplete blood countErythrocyte sedimentation rateThyroid function testsAspartate aminotransferase levels

Other studies may include the following:

ElectrocardiographyAntinuclear antibody levelsGenetic testingElectromyographyMagnetic 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 casesDrug therapyPhysical therapyBracingSurgery

See Treatment for more detail.

NextBackground

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 with attention to airway and aspiration precautions and providing supportive care are indicated while inpatient consultation and detailed studies are performed.

PreviousNextPathophysiology

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, 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.[3]

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.

PreviousNextMortality/MorbidityMorbidity 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.Race

Thyrotoxic hypokalemic periodic paralysis is known to occur in Asian men, and one study suggests that Polynesians are also at risk for this condition.[4]

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