Background
Fatigue has high priority for persons with rheumatoid arthritis (RA) [
1‐
3], and besides pain is cited as the most prominent symptom of the disease [
4‐
6]. The reported prevalence of fatigue in RA varies from 42 to 80 % [
4,
5,
7,
8]. Severe fatigue is reported by about 50 % of persons with RA [
7,
8].
Persons with RA describe fatigue as multidimensional, overwhelming, and unpredictable, with physical, cognitive, and emotional components. The fatigue associated with RA is distinct from normal fatigue in that it is often extreme, unexpected, and not restored by sleep; as such, it affects everyday tasks and social roles [
3,
6,
9].
Fatigue impacts individuals differently, and management strategies vary [
10]. Women report higher levels of fatigue than men [
4,
11,
12], in particular younger women who have to undertake multiple daily roles [
10]. Persons of working age are likely to have multiple daily roles and high demands in life, and are thereby more vulnerable to the impact of fatigue [
10]. The duration and frequency varies among individuals [
3], with studies reporting increasing fatigue as the day passes [
13,
14]. Inconsistent results regarding changes in fatigue have been reported in longitudinal studies based on a single baseline assessment and a single follow-up assessment 1 year later. Applying this method, some studies found stable fatigue levels [
8,
15] and others found variations [
16]. When studying possible fluctuations in fatigue, it appears evident that fatigue should be assessed more frequently than twice a year. Previous studies also indicate inconsistent results regarding seasonal variations in RA; a Japanese study reported seasonal variations in disease activity [
17], while a Canadian study found no seasonal variation in pain and global severity [
18]. To our knowledge, no longitudinal study has investigated seasonal variations in fatigue in persons with RA.
As fatigue negatively impacts life in persons with RA, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group recommends that measurements of fatigue should be included in RA clinical trials [
2]. Traditionally, fatigue is measured by single items assessing general fatigue, such as a one-dimensional visual analogue scale (VAS). Other instruments measure multiple aspects of fatigue including consequences and impacts. Such multi-dimensional fatigue measures incorporate sub-scores measuring, for example, physical and cognitive aspects of fatigue [
19]. However, little is known about fluctuations in fatigue over time and season as measured by general VAS ratings and multi-dimensional rating scales. A recent review article concluded that most studies of fatigue are cross-sectional, and there is a need for longitudinal studies that measure fatigue adequately and regularly over time [
20].
The aim of the present study was to investigate variations in fatigue levels reported by persons with RA of working age at seven different time points during the four seasons. Both a single-item and a multi-dimensional fatigue instrument were used to explore: i) how fatigue levels vary over time ii) how the different aspects of fatigue vary and iii) whether there are any seasonal variations in fatigue levels. The analyses were adjusted for sex and age. Our hypothesis is that fatigue fluctuates over time, when measured regularly over one year.
Discussion
The results of this longitudinal study revealed statistically significant monthly variations in levels of general fatigue, both rated on the single-item VAS fatigue and rated on the multi-dimensional BRAF-MDQ total score. In addition, participants reported significant monthly variations in the Physical, Living, and Cognitive dimensions of fatigue included in the BRAF-MDQ. We also found a significant seasonal variation, with the most severe fatigue in winter, in the four measurements assessing general and physical dimensions of fatigue. Interestingly, the mental dimensions of fatigue did not show seasonal differences. These results support the use of multi-dimensional measures of fatigue. From the perspective of patients, as well as that of professionals, this information can be helpful in developing strategies to handle fatigue, such as providing adequate information about expected fluctuations in fatigue and suggestions about physical activity during the winter months.
The majority of the participants in this study were either working or studying; this means that they were likely to take a summer vacation, which may have contributed to the lower fatigue scores recorded during the summer and early autumn. The study was carried out in Sweden, a country with large variations in temperature and hours of daylight between winter and summer, and so several factors related to living might have influenced fatigue levels, such as outdoor activities and enjoying nature. Physical activity is inversely associated with fatigue [
29,
30], and the level of physical activity has been shown to be highest in spring and summer [
31]. This may be one reason why the physical but not the mental aspects of fatigue decreased during summer. Levels of vitamin D might also have had an influence: a British study found that 13 % of people with RA had a vitamin D deficiency, and a further 50 % had unsatisfactory levels of vitamin D during winter [
32]. Pain and depressive mood have been suggested to be associated with fatigue [
20], but no seasonal variations in pain or depression have been detected in RA [
18,
33]. Further research is needed regarding seasonal influence and possible predictors of the variations in fatigue over time.
The changes in fatigue were statistically significant but the clinical value of these changes needs to be considered. The minimal clinically important difference in the 0–100 VAS fatigue score is suggested to be 10 mm [
34,
35]. The mean seasonal change was within the 10 mm limit, while in some cases the change between two separate months (in particular, January and September) was larger than 10 mm and considered to be of clinical importance. Regarding the BRAF-MDQ total score, the minimum change to indicate a clinically important improvement is suggested to be 7.43 points, while a decrease of 2.58 points indicates a deterioration [
28]. The changes in fatigue in our material were within the 7.43 point limit, and therefore do not indicate a clinically important difference.
The mean value of fatigue rated on the VAS (51 ± 13) was in line with previous research on fatigue in RA [
7]. However, the mean fatigue in a large international study was below 40 [
36]. The large range of baseline fatigue ratings (0–92) indicates the representativity of the study group. The study population comprised three times more women than men, which corresponds to the prevalence of RA in the general population [
37]. Monthly and seasonal variations in fatigue were similar in men and women, although the women tended to report higher numerical fatigue values than men for all fatigue measures. However, due to the relatively low number of men enrolled, caution must be taken when interpreting for differences related to sex.
We also found that age had no significant impact on the levels of fatigue reported over time. Because there was no linear relationship between age and fatigue (Table
2), age was entered into the analysis as a categorical variable (four different age groups) rather than a continuous variable. The age group containing the youngest participants was wider than the others (20–46 years of age), due to the low number of younger participants. The conclusions regarding this group are therefore less precise, and should be studied further. As all participants were of working age, no data were collected for persons older than 65–66 years. Previous studies have reported both significant [
38] and non-significant [
15] correlations between age and fatigue.
This study has several limitations, such as the small sample size. Another is the lack of a healthy control group; similar time-related changes in fatigue levels may also occur in healthy individuals. Most participants ended their participation in August or September, meaning there were few observations in October (
n = 9), and so we chose to omit the October estimates from Fig.
3.
One strength of this study lies in the use of a longitudinal design. As measurements were taken at seven time points over the course of the study, we were able to detect variations in fatigue. Levels of severe fatigue were reported by approximately half of the study population, implying that chronic fatigue is a substantial problem in persons with RA. The present study is the first to identify natural variations in fatigue levels over time and according to season in persons with RA. Further studies are needed to search for factors that influence fatigue in RA over time.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
CF worked on the study design, had the main responsibility for the data collection and manuscript writing, and participated in the statistical analyses and interpretation of the data. AG had the main responsibility for the statistical analyses and interpretation of the data. HF was involved in the study design, statistical analyses, and interpretation of the data. LJ was involved in the study design, statistical analyses, and interpretation of the data. KM had the main responsibility for the study design and participated in the statistical analyses and interpretation of the data. All authors were involved in drafting the article and revising it critically for important intellectual content. All authors approved the final version of the article.