Where should a patient with elevated Creatine Phosphokinase (CPK) and leg pain be referred?

Referral for Elevated CPK and Leg Pain

Refer patients with elevated CPK and leg pain to rheumatology or neurology urgently, as this presentation requires specialist evaluation to distinguish between inflammatory myopathy, medication-induced myopathy, and benign causes. 1

Immediate Referral Criteria (Urgent Rheumatology or Neurology)

Refer urgently if any of the following are present:

• Muscle weakness, particularly proximal muscles (difficulty rising from chair, climbing stairs, lifting arms overhead) 1, 2
• CK ≥3× upper limit of normal (ULN) with symptoms 1, 2
• Any cardiac involvement (elevated troponin, ECG abnormalities, chest pain) - requires immediate cardiology consultation and potential hospitalization 1, 3
• Dysphagia, dysarthria, dysphonia, or dyspnea - these are red flags for severe myositis requiring hospitalization 2, 3

Emergent Hospitalization Criteria

Hospitalize immediately for:

• CK >10× ULN with muscle symptoms 1, 2
• Severe weakness limiting mobility or self-care 1
• Respiratory muscle involvement or difficulty swallowing 1
• Signs of rhabdomyolysis (myoglobinuria, acute kidney injury) 2, 3

Outpatient Rheumatology/Neurology Referral

Refer for outpatient specialist evaluation if:

• CK elevation persists >4 weeks despite conservative management 2, 3
• Progressive symptoms even without frank weakness 2, 3
• CK 3-10× ULN with moderate symptoms (Grade 2 myositis) 1
• Diagnostic uncertainty requiring EMG, muscle MRI, or biopsy 1, 2

Special Considerations Before Referral

Medication Review

• Discontinue statins immediately if CK >5× ULN with symptoms 2, 3
• Hold immune checkpoint inhibitors if CK ≥3× ULN with symptoms - may require permanent discontinuation 1
• Consider other myotoxic medications (fibrates, antipsychotics, tyrosine kinase inhibitors) 3

Initial Workup to Complete Before or Concurrent with Referral

Essential laboratory tests:

• Complete muscle enzyme panel (CK, aldolase, AST, ALT, LDH) 1, 2
• Inflammatory markers (ESR, CRP) 1, 3
• Troponin and ECG to exclude myocardial involvement 1, 3
• Comprehensive metabolic panel and urinalysis for rhabdomyolysis 2, 3
• Autoimmune panel (ANA, RF, anti-CCP) if myositis suspected 3

Conservative Management for Mild Cases (CK <3× ULN, No Weakness)

If CK is mildly elevated without weakness, you may monitor without immediate referral:

• Provide analgesia with acetaminophen or NSAIDs 1, 2
• Advise rest from strenuous activity 2, 3
• Recheck CK, ESR, CRP in 1-2 weeks 2, 3
• Refer to rheumatology/neurology if symptoms persist beyond 4 weeks or any weakness develops 2, 3

Critical Pitfalls to Avoid

• Never attribute CK elevation solely to exercise without excluding pathological causes, especially if elevation persists >1-2 weeks 2, 3
• Never continue statins when CK >10× ULN with symptoms - this risks progression to rhabdomyolysis 2
• Never delay referral for progressive weakness - immune checkpoint inhibitor myositis can be rapidly fatal 2
• Always check troponin - myocarditis accompanying myositis requires immediate therapy discontinuation 1, 3