Mitochondrial Dysfunction May Contribute to SLE Fatigue

Patients with systemic lupus erythematosus (SLE) commonly experience fatigue, and a recent case-control study identified skeletal muscle mitochondrial dysfunction as a possible cause.

“Patients [with SLE] describe multiple dimensions of fatigue and therefore its etiology is likely to be complex,” according to the researchers. “Developments in MRI technology offer a noninvasive opportunity to comprehensively quantify skeletal muscle pathology at both metabolic and structural levels.”

Inactive SLE patients with chronic fatigue were age- and sex-matched to healthy controls. All patients underwent a 3T whole body MRI scan and microstructural sequences (T1‐weighted anatomical images, T2 mapping and diffusion tensor imaging). Using resting and dynamic Phosphorous Magnetic Resonance Spectroscopy (MRS) of the calf muscles, researchers determined phosphocreatine recovery half time (PCr), a mitochondrial dysfunction marker.

Among a total of 37 patients (mean age, 43.8 years; 89.2% female), 19 had SLE. Compared to the healthy controls, SLE patients had a greater risk for physical fatigue, pain, depression, and sleep disturbance (p<0.0001). SLE patients had greater PCr (p=0.045) than the control group (33 seconds vs. 27.1 seconds); among the SLE patients, though, PCr was not associated with physical fatigue (r=‐0.28, p=0.25) or mental fatigue (r=0.2, P=0.41).

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

In another recent study, published in the journal Lupus, researchers evaluated six variables and determined their contribution to fatigue in lupus patients: disease activity, insomnia, depression, stress, pain and physical health. They found that the two most impactful factors were stress (β 0.77, 95% CI 0.17–1.38, p=0.01) and depression (β 0.66, 95% CI 0.21–1.10, p=0.005). Disease activity, sleep, and physical health were not associated with fatigue. In a stepwise regression analysis, researchers found that stress, depression, and pain were responsible for 56% of pain.

Researchers for the present study said that future research is needed.

“Learning from other chronic diseases, the investigation of central mechanisms using advanced MRI brain techniques appears to offer greater potential,” they wrote.

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Sources: MedPage Today, Arthritis Care & Research, Lupus