Fatigue beyond inflammation in inflammatory rheumatic diseases: a narrative review and treatable-traits framework

Fatigue frequently persists after clinically visible inflammation has improved in inflammatory rheumatic diseases (IRDs). This narrative review integrates evidence updated through 21 July 2026 on mechanisms, assessment, and management of fatigue in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's disease (SjD). Across these conditions, associations between fatigue and conventional inflammatory measures are inconsistent and usually weaker than associations with pain, sleep disturbance, mood symptoms, disability, central pain sensitivity, comorbidity, medication effects, and reduced activity tolerance. Recent quantitative findings reinforce this mismatch. In a 2026 RA cohort of 253 patients, 80% reported fatigue and 10% had severe fatigue; fatigue remained present in some patients in remission. In an international survey of 1,155 people with SjD, physical fatigue was among the most frequent symptoms, while mean work and activity impairment reached 46.6% and 48.4%, respectively. Longitudinal RA data showed that improvement in self-reported central pain sensitivity tracked improvement in fatigue, whereas inflammatory markers and imaging were not consistently associated with fatigue. Recent SLE imaging findings also linked region-specific cerebellar alterations with fatigue and cognitive dysfunction, although no central or metabolic biomarker is ready for routine use. Immune-targeted therapies produce variable, generally small-to-moderate fatigue improvements, whereas personalized exercise, rehabilitation, cognitive-behavioural or self-management interventions, and treatment of sleep disorders have supportive clinical evidence. The mismatch between inflammatory remission and continuing fatigue is framed as a fatigue remission gap. This is a practical signal, not a validated diagnosis, and should prompt direct fatigue measurement and a treatable-traits assessment rather than automatic escalation of immunosuppression. The proposed framework sequentially evaluates disease activity, fatigue severity, pain and fibromyalgia overlap, sleep, mood, comorbidities, medication effects, and deconditioning, then selects a shared, modifiable treatment target for reassessment.