What is the recommended workup for a patient presenting with chronic fatigue?

Recommended Workup for Chronic Fatigue

For patients presenting with chronic fatigue, a structured evaluation should begin with screening for severity using a 0-10 numeric rating scale or categorization as none, mild, moderate, or severe, with scores of 4 or greater (moderate to severe) warranting a comprehensive workup. 1

Initial Assessment

• Screen all patients using a numeric rating scale (0-10) or categorization as none/mild/moderate/severe 2
• Patients with scores of 0-3 (mild) require no further assessment; rescreening at regular intervals is sufficient 2
• Patients with scores of 4-10 (moderate to severe) warrant a more focused evaluation 2, 1
• Patients with scores ≥7 typically experience a marked decrease in physical functioning 2

Focused History and Physical Examination

• Assess onset, pattern, duration, and changes in fatigue over time 2, 1
• Document interference with normal functioning and daily activities 1
• Evaluate for associated symptoms such as:
  • B symptoms (fever, drenching night sweats, unexplained weight loss >10% over 6 months) 3
  • Pain, which commonly clusters with fatigue 1
  • Sleep disturbances 1
  • Cognitive difficulties 4
• Review all current medications, supplements, and substances that may contribute to fatigue 2, 1
• Perform a targeted physical examination focusing on:
  • Cardiopulmonary assessment 5
  • Neurological examination 5
  • Skin examination 5
  • Lymph node evaluation 3
  • Assessment for hepatosplenomegaly 3

Laboratory and Diagnostic Testing

• Complete blood count with differential to evaluate for anemia, infection, or malignancy 3, 6
• Comprehensive metabolic panel to assess liver, kidney function, and electrolytes 3
• Thyroid function tests (TSH) 3, 6
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to evaluate for inflammation 3
• Consider additional testing based on clinical suspicion:
  • HIV testing 3
  • Tuberculosis screening (IGRA or TST) if risk factors present 3
  • Chest X-ray if pulmonary symptoms are present 3
  • Advanced imaging (CT or PET/CT) if lymphoma or other malignancy is suspected 3

Assessment of Treatable Contributing Factors

• Screen for emotional distress, depression, and anxiety, which frequently co-occur with fatigue 1, 4
• Evaluate sleep quality, quantity, and hygiene 1, 7
• Assess for medication side effects as potential contributors to fatigue 1
• Screen for alcohol/substance use 1
• Consider underlying medical conditions that may cause fatigue:
  • Endocrine disorders (hypothyroidism, diabetes) 6
  • Autoimmune conditions 6
  • Malignancy 3
  • Infections 4
  • Cardiac or pulmonary disease 5

Special Considerations

• If initial laboratory results are normal, repeated testing is generally not indicated unless new symptoms develop 6
• Consider myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) if fatigue persists for >6 months with postexertional malaise and other characteristic symptoms 5, 4
• For cancer survivors, evaluate for disease recurrence or treatment effects as potential causes of fatigue 2
• Recognize that fatigue rarely occurs in isolation and often clusters with other symptoms 1
• Be aware that laboratory studies affect management in only about 5% of fatigue cases 6

Management Approach

• Develop a structured plan for regular physical activity with stretching and aerobic exercise, except in cases of suspected ME/CFS where exercise may worsen symptoms 5, 6
• Address sleep hygiene and establish consistent sleep patterns 2, 7
• Consider cognitive behavioral therapy for chronic fatigue 8, 4
• Treat any identified underlying medical conditions 5
• Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 6