Fatigue in inflammatory rheumatic diseases: current knowledge and areas for future research

Fatigue is a complex phenomenon and an important health concern for many people with chronic inflammatory rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, primary Sjogren syndrome and systemic lupus erythematosus. Although some clinical trials have shown the benefits of cognitive behavioural therapy in fatigue management, the effect of this approach is relatively modest, and no curative treatment has been identified. The pathogenesis of fatigue remains unclear. Despite many challenges and limitations, a growing body of research points to roles for the immune system, the central and autonomic nervous systems and the neuroendocrine system in the induction and maintenance of fatigue in chronic diseases. New insights indicate that sleep, genetic susceptibility, metabolic disturbances and other biological and physiological mechanisms contribute to fatigue. Furthermore, understanding of the relationships between psychosocial factors and fatigue is increasing. However, the interrelationships between these diverse mechanisms and fatigue remain poorly defined. In this Review, we outline various biological, physiological and psychosocial determinants of fatigue in inflammatory rheumatic diseases, and propose mechanistic and conceptual models of fatigue to summarize current understanding, stimulate debate and develop further research ideas. Fatigue is a common and debilitating symptom of inflammatory rheumatic diseases, but the underlying mechanisms remain poorly understood. In this Review, the authors examine the potential contributing factors, present putative models of fatigue and discuss challenges for research and treatment.

Automated summary

Fatigue is a significant health concern for individuals with chronic inflammatory rheumatic diseases, but its underlying mechanisms remain unclear. Research suggests roles for the immune system, nervous systems, and psychosocial factors in fatigue, but the interrelationships between these mechanisms are still poorly defined. Further study is needed to better understand and address fatigue in this population.