Measures of Fatigue in Patients With Rheumatic Diseases: A Critical Review

Fatigue is a common symptom, with reported prevalence in the population ranging from 7% to approximately 45% (1–5). For example, evidence regarding fatigue prevalence among the US adult population dates back to the 1970s and early 1990s (2,6); a US survey in 1974 showed that 14.3% of men and 20.4% of women reported suffering from frequent fatigue (2), and another study found that 12% of men and 22% of women were considered to have lack of energy (6). The prevalence of fatigue in rheumatic diseases varies significantly. For example, in rheumatoid arthritis (RA), its frequency depends primarily on the criteria used to define it. However, clinically relevant fatigue is reported to occur in 40% to 80% of patients with rheumatic diseases (7–9), with 40% experiencing persistent severe fatigue (10). Around onethird of patients with ankylosing spondylitis (AS) experience severe fatigue (11), with an overall prevalence of 53% to 76% (11–13). In osteoarthritis (OA), the prevalence of fatigue varies between 41% (9) and 56%, with 10% of patients experiencing severe fatigue (14). Fatigue has been described as difficulty in initiating or sustaining voluntary activities (15,16). It is influenced by several factors, including age, sex, physical condition, food intake type, time elapsing between meals, mental status, psychological conditions, personality type, life experience, and health status (17). Fatigue differs depending on whether the individual is healthy or not (18,19). In healthy individuals, fatigue is a predictable and transient physiologic reaction to prolonged intense activity that abates significantly with rest (19). In contrast, individuals with diseases describe fatigue as an overwhelming sense of tiredness at rest, exhaustion with activity, and lack of energy that precludes them from performing their daily tasks (18). Fatigue is common in many rheumatic conditions (20–22). Because it is a subjective clinical manifestation, fatigue can only be evaluated using patientreported outcome measures (PROMs); many measures of fatigue have been used in rheumatology populations (23). The Outcome Measures in Rheumatology consortium (24) endorsed the measurement of fatigue in clinical observational, longitudinal studies (25) and clinical trials, mainly in patients with RA and patients with fibromyalgia syndrome (FMS) (25,26). Different fatigue measures address different aspects of fatigue. For example, as a screening tool, multiitem PROMs can explore broader fatigue issues to create a global score or multidimensional PROMs can produce subscale scores for a range of different facets or domains of fatigue (eg, cognitive and physical fatigue). Multidimensional PROMs with subscales may be useful for informing or evaluating interventions or exploring fatigue causality. Some fatigue PROMs relate to severity only, whereas others include items of both severity and impact (23). Surprisingly, studies of fatigue in inflammatory rheumatological conditions largely fail to show a correlation with measures of inflammation or disease activity. Studies evaluating the relationship of fatigue PROMs with inflammatory markers have found weak associations (8,27). Very strong associations (eg, more than 0.75) might be expected when examining criterion validity with other fatigue scales (21,22). Additionally, reliability of fatigue PROMs can be problematic to evaluate because of the fluctuating and unpredictable nature of fatigue itself (23). The characteristics of an ideal fatigue assessment instrument include being easy to understand and complete, causing minimal burden to users, and being able to discriminate cases from noncases with acceptable levels of sensitivity and specificity. Additionally, it should provide a full description of severity and impact, with the ability to act as an outcome measure sensitive to change regarding disease progression and/or treatment. Moreover, it should be reliable, have good reproducibility, and be stable among raters and over time. It must have a stable structure measuring