What is the approach to a fatigue workup?

Approach to Fatigue Workup

The initial assessment of fatigue should include screening all patients using a numeric rating scale (0-10) or categorization as none, mild, moderate, or severe, with patients scoring 4-10 (moderate to severe) requiring a focused evaluation. 1

Initial Assessment

• Screen all patients using a numeric rating scale (0-10) or categorize as none, mild, moderate, or severe 1
• Patients with scores of 0-3 (mild) require only rescreening at regular intervals 1
• Patients with scores of 4-10 (moderate to severe) warrant a more focused evaluation 1
• Patients with scores ≥7 typically experience a marked decrease in physical functioning 1

Focused History and Physical Examination

• Conduct a thorough review of systems to identify affected organ systems 1
• Document onset, pattern, duration, and changes in fatigue over time 1
• Identify associated or alleviating factors 1
• Assess interference with normal functioning and daily activities 1
• Consider patient's self-assessment of potential causes 1
• Evaluate for B symptoms (fever, drenching night sweats, unexplained weight loss >10% of total body weight over 6 months) 2
• Assess for associated symptoms such as cough, dyspnea, pruritus, and lymphadenopathy 2

Laboratory Studies

• Complete blood count with differential to evaluate for cytopenias, leukocytosis, or abnormal cells 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess inflammation 2
• Blood chemistry, including liver enzymes, alkaline phosphatase, lactate dehydrogenase, and albumin 2
• Thyroid-stimulating hormone (TSH) to rule out thyroid dysfunction 2
• Consider HIV testing and tuberculosis screening (IGRA or TST) in appropriate clinical contexts 2

Imaging Studies

• Chest X-ray as initial screening for pulmonary pathology when indicated 2
• Consider contrast-enhanced CT scan of neck, chest, and abdomen if lymphadenopathy, organomegaly, or masses are suspected 2
• Consider PET/CT scan if lymphoma is suspected 2

Assessment of Treatable Contributing Factors

• Evaluate and treat pain effectively as it commonly clusters with fatigue 1
• Screen for depression and anxiety, which frequently co-occur with fatigue 1
• Assess sleep quality, quantity, and hygiene 1
• Review medications for potential side effects contributing to fatigue 1
• Screen for alcohol/substance use that may contribute to fatigue 1

Classification and Management Approach

• Classify fatigue as physiologic, secondary, or chronic 3
• For physiologic fatigue, address sleep hygiene, diet, and energy balance 3
• For secondary fatigue, treat the underlying condition 3
• For chronic fatigue, consider cognitive behavior therapy, exercise therapy (except in ME/CFS), and symptom management 3
• For ME/CFS, recognize postexertional malaise as the cardinal symptom and avoid recommending exercise that may trigger symptoms 3

Special Considerations

• For cancer survivors, consider disease recurrence or treatment effects as potential causes 1
• Fatigue rarely occurs in isolation and often clusters with other symptoms 1
• Sleep disorders, depression (18.5%), and excessive psychosocial stress are among the most common causes of persistent fatigue 4
• Previously undiagnosed cancer is a rare cause of fatigue (0.6%) 4
• If diagnosis remains unclear after initial workup, schedule regular follow-up visits rather than sporadic urgent appointments 5

Common Pitfalls to Avoid

• Overlooking medication side effects as potential contributors to fatigue 1
• Excessive focus on somatic causes leading to overdiagnosis when initial workup is negative 4
• Repeated laboratory testing when initial results are normal (affects management in only 5% of patients) 5
• Failure to recognize ME/CFS and inappropriately recommending exercise, which can worsen symptoms 3