Fatigue in Systemic Lupus Erythematosus

Grace E Ahn; Rosalind Ramsey-Goldman

Int J Clin Rheumatol. 2012;7(2):217-227.

Abstract and Introduction

Abstract

Systemic lupus erythematosus is a chronic inflammatory autoimmune disease often characterized by fatigue, with significant effects on physical functioning and wellbeing. The definition, prevalence and factors associated with fatigue, including physical activity, obesity, sleep, depression, anxiety, mood, cognitive dysfunction, vitamin D deficiency/insufficiency, pain, effects of medications and comorbidities, as well as potential therapeutic options of fatigue in the systemic lupus erythematosus population are reviewed. Due to variability in the reliability and validity of various fatigue measures used in clinical studies, clinical trial data have been challenging to interpret. Further investigation into the relationships between these risk factors and fatigue, and improved measures of fatigue, may lead to an improvement in the management of this chronic inflammatory disease.

Introduction

The prevalence of systemic lupus erythematosus (SLE) in the USA is estimated to be 15–50 per 100,000 population.^[1] There is variability in the reliability and validity of various fatigue measures used in clinical studies. There are also inconsistent findings regarding the usefulness of biomarkers and imaging studies as measures of fatigue in SLE that we also discuss. Finally, we present the knowledge gaps where further research is needed to more precisely measure fatigue to facilitate efficacy assessments of the treatments for fatigue.

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Executive Summary

Systemic Lupus Erythematosus & Fatigue

A total of 53–80% of systemic lupus erythematosus (SLE) patients identify fatigue as one of their primary symptoms. Fatigue results in decreased quality of life, increased risk of work disability and increased healthcare costs.

Factors Associated With Fatigue

SLE patients' aerobic capacity is often decreased compared to healthy controls and studies have shown improved health outcomes including decreased fatigue from increasing physical activity.
Obesity is prevalent in the SLE population, with a BMI above 30 kg/m ² associated with worse depression and fatigue.
A bidirectional relationship exists between fatigue and poor sleep, with SLE cohorts usually experiencing more sleep–wake disturbances and unrestorative sleep.
Depression has been consistently associated with fatigue and anxiety and mood disorders have been correlated with fatigue in SLE patients compared to healthy controls.
Suboptimal levels of vitamin D have been reported in the SLE population, with vitamin D deficiency correlating with worse fatigue.
There is a positive correlation between pain intensity and fatigue in the SLE population.
No significant associations were found between corticosteroids or NSAID use and fatigue severity.
Coexisting fibromyalgia, thyroid disease and anemia may also affect fatigue in SLE.
Conflicting theories exist, with one side showing positive correlation between SLE disease activity and fatigue, and the other arguing for weak or no association.

Measurements of Fatigue

Over 30 scales exist to test fatigue as a research tool.
Various serum biomarkers for inflammation have been evaluated for their association with fatigue in SLE, including antiphospholipid antibodies, transforming growth factor-β, TNF-α, IL-2, IL-6 and IL-10, with few studies showing positive correlations.
There have been inconsistent findings correlating the association of levels of fatigue to changes of brain imaging using different modalities including MRI and single-photon emission computed tomography.

Therapeutic Trials

Different therapies have been studied to improve fatigue in SLE: psychoeduational intervention to increase wellbeing, computer gaming modules to increase physical activity, acupuncture to decrease fatigue and pain and medication trials with dehydroepiandrosterone, belimumab, and vitamin D3, with some showing positive results.

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