The aetiopathogenesis of fatigue: unpredictable, complex and persistent

Chronic fatigue syndrome is a common condition characterized by severe fatigue with post-exertional malaise, impaired cognitive ability, poor sleep quality, muscle pain, multi-joint pain, tender lymph nodes, sore throat or headache. Its defining symptom, fatigue is common to several diseases. Research has established a broad picture of impairment across autonomic, endocrine and inflammatory systems though progress seems to have reached an impasse. The absence of a clear consensus view of the pathophysiology of fatigue suggests the need to switch from a focus on abnormalities in one system to an experimental and clinical approach which integrates findings across multiple systems and their constituent parts and to consider multiple environmental factors. We discuss this with reference to three key factors, non-determinism, non-reductionism and self-organization and suggest that an approach based on these principles may afford a coherent explanatory framework for much of the observed phenomena in fatigue and offers promising avenues for future research. By adopting this approach, the field can examine issues regarding aetiopathogenesis and treatment, with relevance for future research and clinical practice.