Workup for Fatigue
Begin by quantifying fatigue severity using a 0-10 numeric rating scale, then stratify your workup based on this score: mild fatigue (0-3) requires only education and periodic rescreening, while moderate to severe fatigue (4-10) warrants a focused evaluation targeting treatable contributing factors rather than extensive laboratory testing. 1, 2
Initial Severity Assessment
- Screen all patients using a numeric rating scale where 0 = no fatigue and 10 = worst fatigue imaginable 3, 1
- Scores of 0-3 indicate mild fatigue and require no further workup—provide education on sleep hygiene and energy management, then rescreen at regular intervals 1
- Scores of 4-6 indicate moderate fatigue and scores of 7-10 indicate severe fatigue, both requiring immediate focused evaluation 1, 2
- Scores ≥7 typically correlate with marked decrease in physical functioning and warrant urgent attention 1, 2
Focused History for Moderate to Severe Fatigue (Scores 4-10)
Fatigue Characteristics
- Document onset, pattern, duration, and changes over time 1, 2
- Identify associated or alleviating factors 1
- Assess interference with normal functioning and daily activities 1
- Evaluate the patient's self-assessment of potential causes 1
Red Flag Symptoms
- Screen for B symptoms: fever, drenching night sweats, unexplained weight loss >10% over 6 months 4
- Assess for pain, pulmonary complaints, and unintentional weight loss 4
- Document any lymphadenopathy, hepatosplenomegaly, or skin manifestations 4
Treatable Contributing Factors (Most Common Causes)
- Sleep disturbance: Evaluate sleep quality, quantity, hygiene behaviors, and screen time before bed—sleep disorders are among the most common causes of persistent fatigue 1, 2, 5
- Emotional distress: Screen for depression (present in 18.5% of cases) and anxiety, which frequently cluster with fatigue 1, 5
- Pain: Assess and document pain severity, as it commonly co-occurs with fatigue 1
- Medications: Complete medication review including over-the-counter drugs, herbal supplements, and vitamins as potential contributors 1, 2
- Alcohol/substance use: Screen for misuse that may contribute to fatigue 1
Special Population Considerations
- For new immigrants or recent travelers: Document country of origin and regions visited to assess for tropical diseases including malaria, tuberculosis, schistosomiasis, and dengue 4
- For cancer survivors: Consider disease recurrence or late treatment effects 1
Laboratory Workup
Initial Screening Tests (Only for Scores 4-10)
- Complete blood count with differential 2, 4, 5
- Comprehensive metabolic panel 2, 4
- Thyroid-stimulating hormone 2, 4, 5
- Erythrocyte sedimentation rate and C-reactive protein for inflammation 2, 4
Important caveat: Laboratory studies affect management in only 5% of patients, and if initial results are normal, repeat testing is generally not indicated 6. Anemia and other organic causes account for only 4.3% of cases, and previously undiagnosed cancer represents only 0.6% of cases 5.
Additional Testing Based on Clinical Context
- Nutritional assessment if dietary deficiencies suspected 2
- Infectious disease screening (malaria, tuberculosis, HIV) for new immigrants or travelers to endemic areas 4
- Imaging studies (chest X-ray, CT) only if red flags are present—avoid "fishing expeditions" 4, 5
Management Approach
Universal Interventions (Regardless of Cause)
- Initiate structured physical activity program: Stretching and aerobic exercise (such as walking) 2-3 times weekly for 30-60 minutes 2, 6
- Improve sleep hygiene: Address sleep disturbances through cognitive behavioral therapy for insomnia if needed 2
- Education and counseling: Provide explanation of fatigue mechanisms and management strategies 3
Treat Identified Contributing Factors
- Manage depression and anxiety with selective serotonin reuptake inhibitors (fluoxetine, paroxetine, or sertraline) if depression is identified 6
- Treat pain effectively 1
- Restore nutritional deficiencies with appropriate supplementation 2
- Address medication side effects by adjusting or discontinuing offending agents 1
- Treat identified infections promptly 4
What to Avoid
- Do not use psychostimulants or dietary supplements as they lack efficacy for fatigue management 4
- Avoid excessive laboratory testing if initial workup is normal—this leads to overdiagnosis 5
- Do not prescribe exercise for patients with postexertional malaise (characteristic of ME/CFS), as it can trigger symptom worsening 7
Follow-Up and Monitoring
- Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 6
- Rescreen at regular intervals for symptom evolution 2
- If diagnosis remains unclear after initial workup, watchful waiting with regularly scheduled follow-up is appropriate rather than pursuing extensive additional testing 2, 5
- Continue monitoring even after treatment completion, as fatigue symptoms can persist 3