Fatigue in systemic lupus: the role of disease activity and its correlates

Abstract

Objectives Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to a variety of negative health outcomes resulting from inflammation in various organ systems. Although treatment continues to advance, fatigue remains one of the most salient, poorly understood and addressed patient complaints. Understanding the mechanisms of fatigue can help guide the development of interventions to improve health outcomes. The aim of this research was to evaluate the contribution of six variables (disease activity, insomnia, depression, stress, pain and physical health) to fatigue in SLE without concomitant fibromyalgia (FM). Methods A total of 116 ethnically diverse, primarily female participants (91%) with SLE, receiving care at university medical centers, completed assessments of disease activity and quality of life outcomes (FACIT-FT, Insomnia Severity Index, Perceived Stress Scale (PSS-4), Pain Inventory, Depression-PHQ-9, and LupusPRO-physical function). All patients met the American College of Rheumatology classification criteria for SLE and did not have a known diagnosis of FM. Multivariate linear and stepwise regression analyses were conducted with fatigue (FACIT-FT) as the dependent variable, and the above six variables as independent variables. Results Mean (SD) age was 39.80 (13.87) years; 50% were African American, 21% Caucasian, 13% Hispanic, 9% Asian and 8% other. Mean (SD) FACIT-FT was 20.09 (12.76). Collectively, these six variables explained 57% of the variance in fatigue. In the multivariate model, depression, stress and pain were significantly and independently associated with fatigue, but not disease activity, sleep or physical health. Stress had the largest effect on fatigue (β 0.77, 95% CI 0.17–1.38, p = 0.01), followed by depression (β 0.66, 95% CI 0.21–1.10, p = 0.005). On stepwise regression analysis, only stress, depression and pain were retained in the model, and collectively explained 56% of the variance in fatigue. All three remained independent correlates of fatigue, with the largest contribution being stress (β 0.84, 95% CI 0.27–1.42, p = 0.005), followed by depression (β 0.79, 95% CI 0.44–1.14, p < 0.001) with fatigue. Conclusion Stress, depression and pain are the largest independent contributors to fatigue among patients with SLE, without concurrent FM. Disease activity, sleep and physical health were not associated with fatigue. The evaluation of stress, depression and pain needs to be incorporated during assessments and clinical trials of individuals with SLE, especially within fatigue. This stress-depression-fatigue model requires further validation in longitudinal studies and clinical trials. Significance and innovation: • Disease activity, sleep, pain, stress, depression, and physical health have been reported individually to be associated with fatigue in lupus. This analysis evaluated the role of each and all of these six variables collectively in fatigue among patients with SLE without a known diagnosis of FM. • Disease activity, sleep and physical health were n...

Longitudinal Study of Fatigue, Stress, and Depression: Role of Reduction in Stress Toward Improvement in Fatigue

“…In spite of these limitations, the study had a number of strengths. The longitudinal design of the study extended previous cross‐sectional findings (19). Our prospective model was tested in a large multiethnic population that included validated measures of both depressive symptoms and perceived stress.…”

“…A high prevalence of fatigue seen in patients with clinically diagnosed depression points toward a relationship between the 2 conditions. Depressed mood has a strong positive association with fatigue in SLE (15,16,19,40,41). Anxiety and depressive symptoms are highly prevalent among patients with SLE and are thought to represent central nervous system involvement, immune dysfunction manifestation, and cognitive processes related to the emotional burden of the disease (39).…”

“…Unfortunately, all previously identified variables were not available in the LOS data set. Previously identified primary correlates of fatigue, however, were included in our model (19). Even so, given the strong overlap with anxiety and stress, including both in future analyses would allow for a comparison of the unique role of clinical anxiety and perceived stress individually.…”

“…The origin of fatigue in SLE is believed to be multifactorial and multidimensional. Identified factors associated with fatigue in SLE include stress (11,12), pain (7,12–15), poor sleep (13,16,17), depression (15,16,18–20), reduced levels of exercise (7,13), helplessness (7,13,20,21), abnormal illness behavior (7,13), and poor perceived social support (13,15). The association of fatigue with disease activity in SLE remains controversial, with some studies showing a positive correlation (7,16–18,22) and others with no significant association (4,13,15).…”

“…Understanding predictors and correlates of fatigue in SLE is key to guiding the development of and to providing effective and efficacious treatment. However, current literature is greatly limited by cross‐sectional methodology, which does not permit causal inferences or longitudinal understanding regarding the etiology of fatigue in SLE (19). Guided by our preliminary study using cross‐sectional data, suggesting a relationship between depression, stress, and fatigue in SLE (19), we undertook this study using a larger SLE cohort to explore our hypothesis that perceived stress and depression would predict fatigue over time, as evaluated through longitudinal study design data.…”