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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...

Even after controlling for disease activity and perceived stress, the relationship between pain and CD was explained by sleep disturbance and depression symptoms. Although these relationships need validation in longitudinal studies with additional measurement modalities, our findings may indicate promising, non-pharmacologic intervention avenues for SLE patients with pain and CD. Specifically, cognitive-behavioral therapies for depression and sleep are known to reduce distress and enhance functioning across various psychosocial domains. Given the symptom burden of SLE, interventions that maximize potential benefits without additional pharmacologic treatments may be of particular utility. This article is protected by copyright. All rights reserved.

Objectives LupusPRO has shown good measurement properties as a disease-specific patient-reported outcome tool in systemic lupus erythematosus (SLE). For the purpose of clinical trials, the version 1.7 (v1.7) domain of Pain-Vitality was separated into distinct Pain, Vitality and Sleep domains in v1.8, and the psychometric properties examined. Methods A total of 131 consecutive SLE patients were self-administered surveys assessing fatigue (FACIT, SF-36), pain (Pain Inventory, SF-36), insomnia (Insomnia Severity Index), emotional health (PHQ-9, SF-36) and quality of life (SF-36, LupusPRO) at routine care visits. Internal consistency reliability (ICR) for each domain was obtained using Cronbach's alpha. The convergent construct validity of LupusPRO domains with corresponding SF-36 domains or tools were tested using Spearman correlation. Varimax rotations were conducted to assess factor structures of the LupusPRO v1.8. Results Mean (SD) age was 40.04 (14.10) years. Scores from the LupusPRO-Sleep domain strongly correlated with insomnia scores, while LupusPRO-Vitality correlated strongly with fatigue (FACIT) and SF-36 vitality. The LupusPRO-Pain domain correlated strongly with pain (SF36 Bodily-Pain, Pain Inventory) scores. Similarly, the LupusPRO domains of Physical and Emotional Health had significant correlations with corresponding SF-36 domains. The ICR for HRQoL and non-HRQoL were 0.96 and 0.81. LupusPRO (domains HRQoL and QoL) scores correlated with disease activity. Principal component analysis included seven factor loadings presenting for the HRQOL subscales (combined Sleep, Vitality, and Pain), and three factors for the NHRQoL (Combined Coping and Social Support). Conclusions LupusPRO v1.8 (including its Sleep, Vitality, and Pain domains) has acceptable reliability and validity. Use of LupusPRO as an outcome measure in clinical trials would facilitate responsiveness assessment.

In contrast to the majority of previous shorter-duration studies, 2 of 14 patients in our series had possible HCV-related worsening of liver disease while on etanercept therapy. Although no firm conclusion can be drawn, it appears that HCV infection can worsen while on etanercept therapy, and therefore, we propose these patients should be monitored serially.