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

Lookup NU author(s): Dr Kristen Davies, Professor Fai NgORCiD



This is the authors' accepted manuscript of a review that has been published in its final definitive form by Nature Research, 2021.

For re-use rights please refer to the publisher's terms and conditions.


© 2021, Springer Nature Limited. 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 Sjögren 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.

Publication metadata

Author(s): Davies K, Dures E, Ng W-F

Publication type: Review

Publication status: Published

Journal: Nature Reviews Rheumatology

Year: 2021

Volume: 17

Pages: 651-664

Online publication date: 01/10/2021

Acceptance date: 27/08/2021

ISSN (print): 1759-4790

ISSN (electronic): 1759-4804

Publisher: Nature Research


DOI: 10.1038/s41584-021-00692-1