Systemic Lupus Erythematosus (SLE) is an episodic, multisystem autoimmune disease with complex pathogenesis and no known cure. Fatigue affects greater than 75% of people with SLE, more than half of which describe fatigue as their most disabling symptom. The aim of the research contained in this thesis was to add to the body of evidence related to fatigue in SLE. Understanding this debilitating symptom more thoroughly will enable clinicians to better meet the needs of patients with SLE.
After completing a thorough narrative literature review it became apparent that there were a number of potential contributing factors to fatigue in SLE that had been relatively unexplored. These included vitamin D deficiency, muscle strength and function and myocardial abnormalities.
The specific topics addressed by the research contained in this thesis:
1. Systematically review the evidence regarding the effect of vitamin D supplementation on muscle strength, particularly in SLE
2. Evaluate the reliability of assessing muscle strength in SLE
3. Explore the relationship between muscle strength, vitamin D status and fatigue in women with SLE compared to healthy controls
4. Compare clinical presentation and health related quality of life in SLE in women with and without fatigue
5. Investigate myocardial abnormalities in SLE patients without clinical evidence of prior myocardial damage and explore the relationship between myocardial abnormalities, fatigue and physical function
Vitamin D in SLE has been the focus of numerous studies with the majority finding that a high percentage of patients are deficient. Recent studies have demonstrated a trend towards deficient vitamin D levels contributing to fatigue in SLE. One theory for this relationship is thought to be related to the effect of vitamin D on muscle. However, there is conflicting evidence as to whether 25(OH)D levels are directly related to muscle weakness. The systematic review (study one) included 17 randomised controlled trials with 5072 participants. None of the studies included participants with SLE. The results supported the well known fact that muscle strength is reduced in people with 25(OH)D levels less than 25nmol/L and that vitamin D supplementation improves strength in this population. Based on studies included in the systematic review, vitamin D supplementation does not have a significant effect on muscle strength in adults with baseline 25(OH)D greater than 25nmol/L.
Prior to the use of any assessment tool, the reliability of the device within the population of interest needs to be established. This enables clinicians to establish ‘real’ change rather than that associated with error. Study two evaluated the test-retest reliability and the degree of measurement error when measuring isometric muscle strength with hand held dynamometry and function using the 1 kg arm lift and 30 second chair stand tests. The results of this study were used to calculate sample size and determine the most reliable strength tests to incorporate into subsequent studies investigating fatigue and muscle strength in SLE.
A cross sectional study (study three) compared fatigue, muscle strength, function and vitamin D levels in 24 women with SLE compared to 21 healthy controls. Women with SLE were weaker, had reduced physical function and higher fatigue levels than the control group. Fatigue was related to exercise tests with an endurance component (such as the 30 second chair stand test) but not vitamin D status or maximal isometric strength in SLE.
Approximately one in six people with SLE do not experience abnormal levels of fatigue. In order to further understand fatigue in SLE, investigating what is protective or unique about those without fatigue may offer insight. Study four included 36 women with SLE and compared the clinical features of those with and without fatigue. Although there was no difference in disease severity between groups, those without fatigue had better health related quality of life and better physical function.
Clinically, myocarditis is diagnosed in approximately 9% of SLE cases. However, subclinical myocardial involvement is more frequent as demonstrated by cardiac magnetic resonance (CMR) imaging with studies reporting abnormal findings in approximately 30% of participants. Identifying patients with subacute myocardial inflammation can be challenging. Patients may be asymptomatic or if symptoms occur they are often non-specific and overlap with symptoms of SLE. Clinical manifestations may include fever, myalgias, palpitations, exertional dyspnoea, reduction in physical capacity and fatigue.
Study five was an exploratory study investigating myocardial abnormalities and the relationship to fatigue and physical function in 20 women with SLE without known coronary artery disease. Contrasting previous studies there was a low incidence of myocardial inflammation and oedema. However a novel technique that has not been reported in SLE before using T1 mapping to measure diffuse fibrosis was utilised and a relationship between shorter post contrast T1 time, higher body mass index and reduced physical function was evident.
The studies included in this thesis add to the body of literature regarding fatigue in SLE and provides direction for future research.