What is the appropriate work‑up and management for a young adult male presenting with generalized myalgia?

Approach to Young Male with Myalgia

Initial Diagnostic Workup

Begin with creatine kinase (CK) and erythrocyte sedimentation rate (ESR) as the most useful screening tests—if either is abnormal, proceed immediately to muscle biopsy, electromyography, muscle strength testing, and exercise testing. 1

Essential History Elements

• Duration and pattern of pain: Determine if pain is acute (days), subacute (weeks to months), or chronic (≥3 months) 2, 3
• Timing relative to exercise: Pain within minutes suggests carbohydrate metabolism defect; pain after prolonged exercise or fasting suggests fatty acid oxidation disorder 4
• Medication exposure: Specifically ask about statins, glucocorticoids, immunologic drugs, antimicrobials, and recent anesthesia (succinylcholine) 3, 5
• Associated symptoms:
  • Weakness (suggests inflammatory myopathy or metabolic disorder) 6
  • Fever and rash (consider Adult-Onset Still's Disease) 2
  • Cramps and myotonia (consider myotonic disorders) 6
  • Dark urine (myoglobinuria suggests rhabdomyolysis) 3, 4

Physical Examination Focus

• Proximal muscle strength testing: Weakness indicates myopathy rather than simple myalgia 3, 6
• Skin examination: Look for heliotrope rash or Gottron's papules (dermatomyositis) 6
• Joint examination: Arthritis suggests systemic inflammatory disease like Adult-Onset Still's Disease 2
• Organomegaly: Hepatosplenomegaly occurs in 50-75% of Adult-Onset Still's Disease cases 2

Laboratory Testing Algorithm

First-tier screening:

• Creatine kinase (CK) 1
• ESR and CRP 2, 1
• Complete blood count with differential 2
• Thyroid function tests 6
• Comprehensive metabolic panel 3

If CK or ESR elevated, add:

• Electromyography (EMG) 1
• Muscle strength and exercise testing 1
• Serum ferritin (if systemic symptoms present—levels >5x normal with <20% glycosylated fraction suggest Adult-Onset Still's Disease) 2

If initial workup negative but symptoms persist:

• Plasma acyl carnitine profile during acute episode (for fatty acid oxidation defects) 4
• Genetic testing panel for metabolic myopathies 4
• Muscle biopsy (if weakness present or CK persistently elevated) 6, 1

Differential Diagnosis by Clinical Pattern

Acute Myalgia (Days)

• Drug-induced myopathy: Recent statin initiation, succinylcholine exposure within 48 hours, or other medications 3, 5
• Viral myositis: Self-limited, associated with systemic viral symptoms 3
• Rhabdomyolysis: Markedly elevated CK (>1000 U/L), myoglobinuria, risk of acute kidney injury 3

Subacute Myalgia (Weeks to Months)

• Inflammatory myopathy: Proximal weakness, elevated CK, abnormal EMG 6
• Endocrine disorders: Hypothyroidism, Cushing's syndrome 6
• Adult-Onset Still's Disease: Fever, rash, arthritis, leukocytosis >15,000/μL, ferritin >1000 ng/mL 2

Chronic Myalgia (≥3 Months)

• Fibromyalgia: Widespread pain in all four quadrants, fatigue, sleep disturbance, normal CK and ESR 7, 8
• Metabolic myopathy: Exercise intolerance, episodic symptoms, may have normal baseline CK 4
• Polymyalgia rheumatica: Age >60 years, shoulder/hip girdle pain, markedly elevated ESR (>40 mm/hr) 2

Management Based on Diagnosis

Drug-Induced Myopathy

• Discontinue offending medication immediately 3
• Switch to alternative agent or consider alternative dosing schedule 3
• Monitor CK weekly until normalized 3
• Refer to neuromuscular specialist if symptoms persist after drug discontinuation 3

Inflammatory Myopathy

• Refer to rheumatology for immunosuppressive therapy 2
• Glucocorticoids are first-line for dermatomyositis/polymyositis 2

Adult-Onset Still's Disease

• Glucocorticoids 12.5-25 mg prednisone equivalent daily as initial treatment 2
• Monitor for complications including hepatic dysfunction and hemophagocytic syndrome 2

Fibromyalgia (if chronic widespread pain confirmed)

• Non-pharmacological first-line: Aerobic and strengthening exercise program 9
• Pharmacological options if inadequate response:
  • Amitriptyline 10-50 mg at bedtime 9
  • Duloxetine 60 mg daily 9
  • Pregabalin 300-450 mg daily 9
• Avoid: Corticosteroids and strong opioids (no efficacy demonstrated) 9

Metabolic Myopathy

• Avoid prolonged fasting and strenuous exercise triggers 4
• Genetic counseling and family screening 4
• Symptomatic treatment with pregabalin, gabapentin, or amitriptyline for myalgic pain 6

Critical Pitfalls to Avoid

• Do not assume fibromyalgia without checking CK and ESR first—specific muscle abnormalities are found in one-third of myalgia patients despite normal initial presentation 1
• Do not miss drug-induced myopathy—onset can be weeks to months after drug exposure, and early recognition prevents progression to rhabdomyolysis 3
• Do not overlook metabolic myopathies in atypical presentations—CPT II deficiency can present with pain after brief exercise, mimicking glycogen storage disorders 4
• Do not delay immunosuppression if hemophagocytic syndrome suspected—pancytopenia in Adult-Onset Still's Disease requires prompt treatment 2