Patient-Reported Fatigue Associated with Joint Histopathology in Rheumatoid Arthritis

Area of Science:

• Rheumatology
• Immunology
• Pathology

Background:

• Fatigue is a significant and poorly understood symptom in rheumatoid arthritis (RA).
• Existing research has not fully elucidated the complex factors contributing to fatigue in RA patients.
• Identifying associations between fatigue and clinical, serological, and histological features is crucial for effective management.

Purpose of the Study:

• To investigate the associations between patient-reported fatigue and clinical features, disease activity, and synovial histology in rheumatoid arthritis (RA).
• To explore the mediating and confounding factors influencing the relationship between RA disease activity and fatigue.

Main Methods:

• Recruited 160 RA patients meeting ACR/EULAR criteria before joint replacement surgery.
• Collected demographic data, RA characteristics, joint counts, ESR, CRP, and fatigue levels (mild, moderate, severe).
• Analyzed synovial tissue histology and used Kendall's tau, directed acyclic graphs (DAGs), and multivariable logistic regression to assess associations.

Main Results:

• Fatigue correlated with disease activity score (DAS28-ESR), synovial lining hyperplasia (SLH), anxiety, depression, and pain.
• DAG analysis revealed pain fully mediated the DAS28-ESR-fatigue link, while anxiety and depression partially mediated it; female sex was a confounder.
• Multivariable models confirmed female sex, DAS28-ESR, and SLH were independently associated with higher fatigue levels.

Conclusions:

• Fatigue in RA is associated with both overall disease activity (DAS28-ESR) and specific synovial pathology (SLH).
• Synovial lining hyperplasia (SLH) is independently associated with fatigue, even when controlling for disease activity.
• These findings highlight the multifactorial nature of RA fatigue, involving systemic inflammation and local joint pathology.