What is the workup for elevated Creatine Kinase (CK)?

From the Guidelines

The workup for elevated creatine kinase (CK) should prioritize a thorough history and physical examination to identify potential causes, followed by discontinuation of any medications that could cause CK elevation, and initial laboratory tests including comprehensive metabolic panel, thyroid function tests, and repeat CK measurement. The approach to elevated CK levels should consider the degree of elevation and the presence of symptoms, as mild asymptomatic elevations may only require observation and repeat testing, while higher levels or symptomatic cases warrant more extensive evaluation 1.

Initial Steps

• Discontinue any medications that could cause CK elevation, particularly statins
• Initial laboratory tests should include:
  • Comprehensive metabolic panel
  • Thyroid function tests
  • Repeat CK measurement
• Consider factors that can influence CK levels, such as ethnicity, body composition, and exercise intensity 1

Further Evaluation

• If CK remains elevated, order:
  • Aldolase
  • Myoglobin
  • Inflammatory markers (ESR, CRP)
  • Autoimmune markers (ANA, anti-Jo-1)
  • Consider viral studies
• Electromyography (EMG) and nerve conduction studies can help differentiate between myopathic and neurogenic processes
• Muscle biopsy may be necessary for definitive diagnosis in cases of persistent unexplained elevation
• Imaging studies like MRI might be indicated for suspected inflammatory myopathies

Considerations

• Monitor renal function as severe CK elevation can cause kidney injury
• The extent of workup should be proportional to the degree of CK elevation and presence of symptoms
• Consider the timing of blood sample collection after exercise, as CK levels may peak between 24 and 120 hours depending on the exercise modality 1
• Be aware of the limitations of using CK levels as a marker of muscle damage, as there is often a poor relationship between functional outcomes and CK activity 1

Management

• For patients with immune-related adverse events, such as myositis, management should follow established guidelines, including holding or discontinuing immune checkpoint inhibitors, and initiating corticosteroids or other immunosuppressants as needed 1
• Consider referral to a rheumatologist or neurologist for further evaluation and management of suspected inflammatory myopathies or other systemic conditions.

From the FDA Drug Label

Discontinue atorvastatin calcium if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the atorvastatin calcium dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.

The workup for elevated CK levels in patients taking atorvastatin calcium includes:

• Discontinuing atorvastatin calcium if markedly elevated CK levels occur
• Monitoring for symptoms of myopathy, such as muscle pain, tenderness, or weakness
• Reporting any unexplained muscle symptoms to a healthcare provider, especially if accompanied by malaise or fever
• Considering alternative diagnoses, such as immune-mediated necrotizing myopathy (IMNM), if CK elevations persist despite discontinuation of atorvastatin calcium 2

From the Research

Workup for Elevated CK

The workup for elevated creatine kinase (CK) levels involves a comprehensive approach to identify the underlying cause. The following steps can be taken:

• Obtain a thorough patient history to assess for acquired and hereditary etiologies 3
• Perform a physical examination to look for signs of muscle weakness or other abnormalities
• Order laboratory tests, including:
  • CK levels to confirm elevation and monitor trends
  • Electrolyte panel to evaluate for electrolyte imbalances
  • Renal function tests to assess for acute renal failure, which can be a complication of rhabdomyolysis 4
  • Liver function tests to evaluate for deranged liver functions
  • Urine tests, such as urine legionella testing and urine toxicology, to identify potential causes of rhabdomyolysis 4
• Consider imaging studies, such as muscle ultrasound or MRI, to evaluate for muscle damage or other abnormalities
• Evaluate for potential causes of elevated CK, including:
  • Rhabdomyolysis, which can be caused by traumatic or non-traumatic factors, such as drugs, toxins, and infections 4, 5
  • Antipsychotic-induced rhabdomyolysis, which can occur in patients taking antipsychotic medications 5
  • Acute myocardial infarction, which can cause elevated CK-MB levels 6
  • Chronic diseases, such as cardiovascular disease, which can cause elevated troponin levels 7

Differential Diagnosis

The differential diagnosis for elevated CK levels is broad and includes:

• Rhabdomyolysis
• Antipsychotic-induced rhabdomyolysis
• Acute myocardial infarction
• Neuroleptic malignant syndrome
• Acute coronary syndrome
• Muscular dystrophy
• Myopathies
• Electrolyte imbalances

Clinical Significance

Elevated CK levels can have significant clinical implications, including:

• Increased risk of renal damage and acute renal failure 4
• Increased risk of mortality in patients with acute myocardial infarction 6
• Need for careful monitoring and management to prevent complications and improve outcomes 5, 3