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

Diagnostic Workup for Chronic Fatigue

Begin by screening fatigue severity using a 0-10 numeric scale, and if the score is ≥4, proceed with a focused evaluation targeting treatable medical conditions and contributing factors rather than extensive laboratory testing. 1

Initial Severity Assessment

• Ask the patient: "How would you rate your fatigue on a scale of 0 to 10 over the past 7 days?" 2, 3
• Scores of 0-3 (mild fatigue) require no further workup—only routine rescreening at regular intervals 2, 3, 1
• Scores of 4-10 (moderate to severe fatigue) warrant immediate focused evaluation 2, 3, 1
• Scores ≥7 typically indicate marked functional impairment and decreased physical functioning 2, 3, 1

Focused History (For Scores ≥4)

Fatigue Characteristics

• Document onset, pattern, duration, and changes over time 3
• Identify associated or alleviating factors 3
• Assess interference with daily activities and normal functioning 3
• Obtain the patient's self-assessment of potential causes 3

Medication and Substance Review

• Perform a complete medication review, as side effects are commonly overlooked as contributors to fatigue 1
• Screen for alcohol and substance use 3, 1
• Review all prescription and over-the-counter medications and supplements 2

Common Treatable Contributing Factors

• Pain assessment: Pain commonly clusters with fatigue and should be treated effectively 3
• Emotional distress screening: Screen specifically for depression and anxiety, which frequently co-occur with fatigue 3, 1
• Sleep disturbance evaluation: Assess sleep quality, quantity, and hygiene 3
• Anxiety symptoms: Evaluate for generalized anxiety disorder 1

Red Flag Symptoms

• Unintentional weight loss 2
• Pulmonary complaints 2
• Persistent pain 2
• Symptoms suggesting disease recurrence or metastatic disease 2

Physical Examination

• Conduct a thorough review of systems to identify affected organ systems 3
• Perform lymph node assessment 1
• Evaluate for hepatosplenomegaly 1

Laboratory Workup

Initial screening tests should be limited and targeted 1:

• Complete blood count with differential 1
• Comprehensive metabolic panel 1
• Thyroid-stimulating hormone 1
• Erythrocyte sedimentation rate 1
• C-reactive protein for inflammation 1

Important Caveats

• Laboratory results affect management in only 5% of patients 4
• If initial laboratory results are normal, repeat testing is generally not indicated 4
• Avoid "fishing expeditions" with extensive testing if medical illness is not evident from history and initial workup 5
• Previously undiagnosed cancer accounts for only 0.6% of cases, and anemia/other organic causes account for only 4.3% 6

Imaging Studies

Imaging should only be pursued if red flags are present 1:

• Chest X-ray (if indicated by symptoms) 1
• CT chest/abdomen/pelvis with contrast (only with red flags) 1
• PET/CT (only with red flags) 1

Special Timing Considerations

• Mild to moderate fatigue persisting 6-12 months after completion of therapy (in cancer survivors) does not warrant extensive workup unless other symptoms are present 2
• Moderate to severe fatigue that begins after or worsens during this period, or when accompanied by other symptoms, warrants more extensive evaluation to screen for metastatic disease or comorbidities 2

Common Pitfalls to Avoid

• Overlooking medication side effects as potential contributors 3, 1
• Pursuing extensive laboratory testing when history and physical examination do not suggest organic disease 1, 5
• Failing to recognize that fatigue rarely occurs in isolation and often clusters with other symptoms 3
• Assuming fatigue must have a somatic cause and pursuing overdiagnosis 6
• Not screening for psychiatric illness (depression accounts for 18.5% of cases) 6