Severe fatigue is associated with diminished lung function and elevated Galectin-9 levels in early systemic sclerosis

Area of Science:

• Rheumatology
• Immunology
• Pulmonology

Background:

• Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like symptoms are common in rheumatic diseases.
• Little is known about fatigue frequency and manifestations in systemic sclerosis (SSc).

Purpose of the Study:

• To investigate the association between severe fatigue and disability, inflammation, and fibrosis in early systemic sclerosis patients.
• To explore potential biomarkers for fatigue in SSc.

Main Methods:

• Cross-sectional study of 51 SSc patients (UofA cohort) and validation in 126 SSc patients (CSRG cohort).
• Assessed disability, disease markers, inflammatory markers, and fibrotic/vascular complications.
• Utilized validated fatigue questionnaires and ME/CFS criteria.

Main Results:

• SSc patients with severe fatigue showed significantly higher disability and reduced lung function.
• Elevated Galectin-9 levels were observed in fatigued SSc patients, correlating with reduced pulmonary function and increased disease damage.
• Indicators of disease progression like reduced nailfold capillary density and elevated VEGF, LTα, and IL-16 were associated with severe fatigue.

Conclusions:

• Severe fatigue in SSc is associated with increased disability, reduced pulmonary function, and vascular remodeling.
• ME/CFS-like symptoms in SSc may indicate sub-clinical inflammation and fibrosis.
• Galectin-9 may serve as a biomarker for stratifying SSc patients, especially those with severe fatigue.