Differential Diagnosis for Generalized Weakness with Elevated CPK

• Single Most Likely Diagnosis
  • Polymyositis: This is an inflammatory muscle disease characterized by progressive weakness and elevated CPK levels. The symptoms and lab findings align closely with this condition, making it a strong candidate for the single most likely diagnosis.
• Other Likely Diagnoses
  • Dermatomyositis: Similar to polymyositis but also includes skin manifestations. The presence of skin symptoms would help differentiate it, but the muscle weakness and elevated CPK are consistent.
  • Muscular Dystrophy: A group of inherited disorders characterized by progressive muscle weakness. While the onset can vary, elevated CPK levels are common, especially in the early stages.
  • Rhabdomyolysis: A serious syndrome due to direct or indirect muscle injury. It results in the death of muscle fibers and release of their contents into the bloodstream, leading to elevated CPK levels and generalized weakness.
• Do Not Miss Diagnoses
  • Acute Myocardial Infarction: Although CPK-MB is more specific for myocardial damage, total CPK can be elevated in myocardial infarction. Generalized weakness could be a presenting symptom, especially in the elderly or those with atypical presentations.
  • Neuroleptic Malignant Syndrome (NMS): A life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic medication. Muscle rigidity and elevated CPK are key features, along with altered mental status and autonomic dysfunction.
  • Malignant Hyperthermia: A rare but life-threatening medical emergency triggered by certain medications used for general anesthesia. It presents with muscle rigidity, high fever, and elevated CPK, among other symptoms.
• Rare Diagnoses
  • Glycogen Storage Diseases: Certain types, like McArdle's disease, can present with muscle weakness and elevated CPK after exercise due to the inability to break down glycogen for energy.
  • Mitochondrial Myopathies: A group of disorders caused by mutations in the mitochondrial DNA affecting muscle and sometimes other tissues. They can present with weakness and elevated CPK, among a wide range of other symptoms.
  • Inflammatory Myopathies due to Other Causes: Such as inclusion body myositis, which is the most common acquired myopathy in adults older than 50 years, characterized by progressive muscle weakness and elevated CPK levels.