Are creatine kinase (CK) levels always elevated in patients with myopathy?

CK Levels Are Not Always Elevated in Myopathy

No, creatine kinase (CK) levels are not always elevated in myopathy—several well-characterized myopathic conditions present with normal or minimally elevated CK levels, making CK an imperfect screening marker for muscle disease. 1

Myopathies with Normal or Minimally Elevated CK

Inclusion Body Myositis

• Sporadic inclusion body myositis characteristically presents with only minimally elevated CK levels despite significant muscle weakness and atrophy, particularly affecting forearm flexors, finger flexors, and quadriceps muscles. 1
• This inflammatory myopathy occurs after age 50 years with a 3:1 male predominance and features insidious onset of asymmetric weakness. 1

Amyopathic Dermatomyositis

• Patients with amyopathic dermatomyositis have the classic dermatomyositis rash but completely normal muscle enzyme levels (including CK) within 2 years after diagnosis, along with normal EMG findings. 1
• These patients can still develop serious complications including interstitial lung disease and malignancy, despite absent CK elevation. 1

Dermatomyositis with Selective Aldolase Elevation

• Dermatomyositis can present with elevated aldolase but normal CK levels, representing a distinct phenotype with unique characteristics. 2
• These patients have less frequent cutaneous involvement (50% vs. 100%) and fibrillation potentials (50% vs. 90.5%) compared to dermatomyositis with elevated CK, but higher erythrocyte sedimentation rates and more common perifascicular mitochondrial pathology. 2
• Approximately 30 different types of myopathies can present with isolated aldolase elevation and normal CK, with most being treatable conditions. 2

Metabolic Myopathies

• Myoadenylate deaminase deficiency presents with cramp-like burning muscle pain and weakness without relevant CK elevation, requiring muscle biopsy and genetic testing for diagnosis. 3
• Metabolic myopathies generally show lower CK elevations compared to Duchenne muscular dystrophy, inflammatory myopathies, and congenital muscular dystrophies. 4

Clinical Implications for Diagnosis

When to Suspect Myopathy Despite Normal CK

• Proximal muscle weakness with normal CK should prompt consideration of inclusion body myositis, amyopathic dermatomyositis, or metabolic myopathies. 1, 3
• Check aldolase, AST, ALT, and LDH levels—these may be elevated when CK is normal, particularly in dermatomyositis. 2
• Inflammatory markers (ESR, CRP) may be elevated in inflammatory myopathies even when CK is normal. 2

Diagnostic Workup Beyond CK

• Muscle biopsy remains the gold standard for confirming myopathy diagnosis when clinical suspicion is high despite normal CK, with 79% sensitivity and 93% specificity. 5
• EMG and muscle MRI can detect myopathic changes even when CK is normal, particularly useful in amyopathic dermatomyositis. 1
• Autoimmune panels (ANA, myositis-specific antibodies including anti-HMGCR) should be checked when inflammatory myopathy is suspected regardless of CK level. 1

Critical Pitfalls to Avoid

• Never exclude myopathy based solely on normal CK levels—the absence of CK elevation does not rule out significant muscle disease, particularly inclusion body myositis, amyopathic dermatomyositis, or metabolic myopathies. 1, 3, 2
• Do not attribute muscle symptoms to "benign" causes without thorough evaluation when weakness is present, even with normal CK—progressive weakness requires urgent evaluation regardless of enzyme levels. 1
• Recognize that CK levels show great individual variability based on age, gender, race, muscle mass, and physical activity, with some individuals being "low responders" with chronically low CK despite muscle pathology. 6