Burden of fatigue in cryopyrin-associated periodic syndromes

Fatigue in cryopyrin-associated periodic syndromes (CAPS) often persists despite controlling inflammation. This study explores fatigue burden, its link to disease activity, and factors tied to chronic fatigue in autoinflammatory conditions.

A single-centre study (2007-2024) of children and adults with CAPS analysed demographics, clinical data, inflammation, treatment, disease activity, and fatigue scores. Relationships between these factors and predictors of chronic fatigue were assessed.

A total of 108 patients with CAPS were included; 53 were female (49%). Median age at diagnosis was 11 years (range, 0-73); median follow-up duration 7 years (range, 1-18). Muckle-Wells syndrome was the most common phenotype (86%). At the time of diagnosis, hearing loss was present in 30%, aseptic meningitis in 6%. At enrolment, fatigue was the most common symptom, affecting 100 patients (93%), with a median fatigue score of 7 (0-10, visual analogue scale); high disease activity was present in 67%. At the last visit, fatigue remained prevalent, reported in 83 (77%), with a median score of 3 (range, 0-10). Importantly, only 4% of patients had high disease activity, whereas 83% had inactive disease. Factors influencing chronic fatigue in CAPS included age at diagnosis (P < .001, Cohen's d = -0.776, β = -2.15), NLRP3 mutation status (P = .009, Cohen's d = -0.516, β = -1.48), disease activity (P < .001), familial CAPS (62% vs 38%, P = .132, Cohen's d = -0.298, β = -0.87), and the COVID-19 pandemic (P < .001).

Fatigue persists in autoinflammatory diseases despite effective disease control. Further research is needed to identify mechanisms and interventions.