Abstract

BackgroundFatigue is one of the most important symptoms of patients with rheumatic and musculoskeletal diseases (RMDs) and numerous studies on fatigue in patients with RMDs have been published. However, no overview exists of all topics relevant to understand and manage fatigue in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA, including psoriatic arthritis (PsA)), osteoarthritis (OA) and fibromyalgia (FM).ObjectivesTo scope published reviews on aspects of fatigue identified by patients in a preceding initiative as relevant for care and mapped to the following research areas: 1) definitions for fatigue, 2) measurement instruments for fatigue, 3) determinants of fatigue, 4) impact of fatigue, and 5) effect of interventions on fatigue in patients with RMDs of interest.MethodsA methodological framework for scoping reviews was followed1. A systematic literature search was performed in five bibliographical databases. Data selection followed by data extraction was done by two independent researchers. Included reviews were categorized in Cochrane reviews (CRs), non-Cochrane systematic reviews (SRs) or narrative reviews (NRs). Data extraction was performed hierarchal based on review type (CRs followed by SRs and NRs) and year of publication. SRs and NRs were excluded if there was overlap in the underlying studies within the reviews. Data synthesis accounted for hierarchy in level of evidence by review type (CRs were considered as best evidence followed by SRs and NRs). For each research area and stratified per type of RMD, a narrative synthesis was performed. Two meetings were organized with a patient panel to discuss the results from a patient perspective.ResultsThe scoping review included 144 reviews (18 CRs, 42 SRs and 84 NRs). RA was addressed most frequently (60/144 (42%)). Fatigue was a secondary outcome in the majority of these reviews.No agreed upon definition for fatigue in any of the RMDs was found. Across reviews, there was agreement that fatigue is a complex multifactorial and highly subjective symptom, including various subtypes with specific characteristics.Reviews discussed 23 generic and 3 disease-specific self-reported outcome instruments to measure fatigue in RA, SpA and FM, but no reviews on outcome instruments for OA were found. Four of these 23 (17.4%) instruments included validated cut-off values to diagnose or classify excessive fatigue.Numerous factors were associated with fatigue (Figure 1), but the study design (often cross-sectional) hindered studying causality. Across RMDs, pain, physical function, and depressive symptoms were the most frequently studied disease related factors; gender and stress the most frequent contextual factors related to fatigue. The strength of association was small or moderate, but mostly not reported.Figure 1.Determinants of fatigue and the related minimal number of underlying studies within reviewsWork disability was one of the most frequently studied consequences of fatigue in RMDs, followed by impact on pain, physical activity and stress. Strength of these associations was not reported.Finally, both pharmacological and non-pharmacological interventions, including physical activity-based and psychological interventions, generally had a small positive effect on fatigue in RMDs. No reviews described the effect of pharmacological interventions on fatigue in OA.All results were relatable for the patient panel and some missing aspects were pointed out. The patient panel advised to develop a research agenda to specifically diagnose and treat excessive fatigue in RMDs, as continuing the current path is likely to increase publications about fatigue, but unlikely to change patients’ lives.ConclusionThis scoping review emphasizes the complexity of fatigue. Only a minority of the reviews had a primary focus in fatigue, whereas to patients this prominent symptom deserves specific attention.

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