Skeletal Muscle Not a Major Factor in Lupus-related Fatigue, Study Suggests

Abnormalities in the skeletal muscle are not a major contributor to the fatigue experienced by systemic lupus erythematosus (SLE) patients, a study based on magnetic resonance imaging (MRI) suggests, contradicting prior beliefs.

The study, “Metabolic and structural skeletal muscle health in systemic lupus erythematosus related fatigue: a multi‐modal magnetic resonance imaging study,” was published in Arthritis Care & Research.

Fatigue is a common problem for SLE patients, with up to 85 percent reporting significant levels that affect quality of life and the ability to work. But little is understood about what causes this symptom in SLE patients.

Previous research with biopsies had suggested that patients with SLE have more structural abnormalities in some muscles. Investigators in the current study aimed to corroborate these data using advanced imaging techniques.

“Developments in magnetic resonance (MR) imaging technology offer a non-invasive opportunity to comprehensively quantify skeletal muscle pathology at both metabolic and structural levels,” they wrote.

They recruited 19 patients with inactive SLE who reported significant fatigue — indicated by a score higher than three on the Chalder Fatigue Scale for at least three months — and impaired muscle strength. They also recruited a group of 18 age- and sex-matched individuals used as controls. The participants were mostly women, with a median age of 43 years.

Compared with the healthy subjects, SLE patients had, on average, significantly higher scores for fatigue, 14.7 versus 6.9 on the Chalder Fatigue Scale; pain, 3.5 versus 0.3 on the 0-10 numeric rating scale; sleep disturbances, 12.7 versus 4.8 on the Jenkin’s Sleep Scale; anxiety, 9.3 versus 4.3 on the Hospital Anxiety and Depression Scale; and depression, 9.3 versus 4.3 on the same scale.

However, MRI analysis showed no structural differences between patients and controls in the skeletal muscles — muscles covering the bones, involved in voluntary movement. And while the skeletal muscle of SLE patients showed some mitochondrial malfunction — meaning they were not producing enough energy — additional measures showed that this did not correlate with levels of physical or mental fatigue in these patients.

“Taken together, skeletal muscle does not appear to serve as a major factor in SLE-related fatigue,” the researchers said.

So, what might be the driving force behind fatigue in SLE? More research still needs to be done, but the investigators point to a recent study in a different autoimmune disease — ANCA-associated vasculitis — in which fatigue did not appear to be affected by skeletal muscle function but rather by a reduced ability to activate muscle and greater perceived effort.

“Together, these observations pointed towards centrally rather than peripherally driven mechanisms,” the researchers concluded, adding that future studies of fatigue in SLE patients should try to look beyond the skeletal muscle.