What is the diagnostic workup for chronic fatigue?

Diagnostic Workup for Chronic Fatigue

The diagnostic workup for chronic fatigue should begin with screening for fatigue severity using a 0-10 numerical rating scale, followed by a focused history, physical examination, and targeted laboratory testing to identify treatable contributing factors. 1

Initial Screening and Assessment

• Use a 0-10 numerical rating scale to assess fatigue severity:

  • 0-3: Mild fatigue (minimal intervention needed)
  • 4-6: Moderate fatigue (requires evaluation)
  • 7-10: Severe fatigue (requires comprehensive evaluation) 1

• For patients with moderate to severe fatigue (score ≥4), proceed with comprehensive evaluation

Focused History Components

1. Fatigue characteristics assessment:

   • Onset, pattern, duration, and changes over time
   • Associated or alleviating factors
   • Interference with daily function and activities 1

2. Review of systems to identify organ systems affected 1

3. Assessment of concurrent symptoms and contributing factors:

   • Pain
   • Emotional distress (depression, anxiety)
   • Sleep disturbance and sleep hygiene
   • Nutrition status
   • Activity level
   • Medication side effects (especially sedating medications)
   • Alcohol/substance use
   • Comorbidities 1

4. Screening for depression using the two-question test:

   • "In the last month, have you often felt dejected, sad, depressed or hopeless?"
   • "In the last month, did you experience significantly less pleasure than usual with the things you normally like to do?" 1

Physical Examination

• Thorough medical examination focusing on:
  • Vital signs (including orthostatic measurements)
  • Cardiopulmonary assessment
  • Neurological examination
  • Lymph node examination
  • Skin examination 1, 2

Laboratory Testing

For moderate to severe fatigue, basic laboratory workup should include:

• Complete blood count (to assess for anemia)
• Comprehensive metabolic panel
• Thyroid function tests (TSH, free T4)
• Inflammatory markers (ESR, CRP)
• Urinalysis
• Additional testing based on clinical suspicion:
  • Iron studies if anemia is present
  • Vitamin B12 and folate levels
  • Viral studies if clinically indicated 1, 2

Special Considerations

• For cancer patients or survivors, evaluate disease status and treatment history 1
• For persistent fatigue >6 months with postexertional malaise, consider myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) using the 2015 National Academy of Medicine diagnostic criteria 2
• If initial laboratory results are normal, repeat testing is generally not indicated 3

Common Pitfalls to Avoid

1. Premature attribution to psychological causes - Ensure thorough medical evaluation before attributing fatigue to depression or anxiety

2. Excessive laboratory testing - Laboratory studies affect management in only 5% of patients; targeted testing based on clinical findings is more efficient 3

3. Recommending exercise for all patients - Exercise can worsen symptoms in ME/CFS patients due to postexertional malaise 2

4. Missing medication side effects - Always review complete medication list, including over-the-counter medications and supplements 1

5. Failure to recognize fatigue clusters - Fatigue rarely occurs alone and commonly clusters with sleep disturbance, emotional distress, or pain 1

By following this systematic approach to evaluating chronic fatigue, clinicians can identify treatable contributing factors and develop appropriate management strategies tailored to the underlying causes.