Is it Really “Just Fatigue” in Patients with Systemic Autoimmune Rheumatic Diseases (SARDs): Applying the Case Definition of Chronic Fatigue Syndrome in Patients with SARDs – A Pilot Study

Objectives Systemic autoimmune rheumatic diseases (SARDs) (eg, systemic sclerosis (SSc) and systemic lupus erythematosus (SLE)) are inflammatory diseases that result in a substantial reduction in quality of life. Patients with SARDs often develop symptoms of fatigue and pain akin to patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). To date, it is unclear how common ME/CFS-like symptoms are in different SARDs. In this pilot study we sought to determine frequency of ME/CFS and FM manifestations in patients with SLE and SSc and to examine severity of associated disability. Methods We conducted a cross-sectional study with SSc (n=49) and SLE (n=38) patients from a single center. Patient-reported outcomes were gathered using validated patient-reported questionnaires that assessed the severity of fatigue, pain, cognitive impairment, disability, quality of life and clinical parameters. Statistical analysis including chi-square and Wilcoxon-rank sum test were carried out using STATA-17 and utilized to link parameters associated with ME/CFS and FM with disease-associated values. Results A total of 25 (51%) SSc patients and 19 (50%) SLE patients were classified as suffering from co-morbid ME/CFS (SSc-CFS and SLE-CFS). ME/CFS in both SSc and SLE was associated with FM and cognitive impairment (p<0.05). SSc-CFS and SLE-CFS patients also had poorer quality of life, greater disability, and more pain compared to non-CFS patients (p<0.001). SSc-CFS was not associated with autoantibodies, CRP, disease duration, or organ damage. Similarly, SLE-CFS was not associated with dsDNA antibody, CRP or disease activity, although it was associated with longer disease duration (p=0.046). A comparison of SSc-CFS and SLE-CFS patients revealed similarities in the degree of disability and associated reduction in quality of life. However, ME/CFS-like symptoms in SSc-CFS and SLE-CFS were different. Specifically, SSc-CFS patients had more severe fatigue, while SLE-CFS patients had more profound cognitive dysfunction - suggesting that biological differences may be present. Conclusion Properties associated with ME/CFS are similar between SSc and SLE patients but not the same, with differences in the severity of fatigue and cognitive impairment. Future confirmation of these findings in larger cohorts, and exploration of their molecular mechanisms may result in a deeper understanding of these symptoms in SARDs. This work may expand on existing work describing the “type 2” lupus subtype with similar symptoms and result in novel therapeutic approaches.

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