Background/Purpose: Fatigue is considered an important disease burden by patients with vasculitis, yet mechanisms underlying fatigue are poorly understood. Physician-derived measures of vasculitis disease activity do not correlate with fatigue. The aim was to determine if fatigue is associated with patient-reported measures of disease activity and/or illness perceptions, defined as the cognitive beliefs that patients have about their illness.

Methods: Participants were recruited from an online patient contact registry in vasculitis. Disease activity (remission vs active), disease extent (presence of a defined severe manifestation), disease duration, remission duration, and clinical variables (age, sex, race, depression, sleep disturbance) were assessed per patient-report. Fatigue was measured using the general subscale of the Multidimensional Fatigue Inventory (MFI) with scores ≥13 indicating severe fatigue. Illness perceptions were assessed using the revised Illness Perception Questionnaire (IPQ-R). The IPQ-R measures illness perceptions in specific dimensions: identity, timeline, timeline-cyclical, consequences, personal and treatment control, emotional representations, and coherence [see Table for definitions]. Disease status, clinical variables, and IPQ-R dimensions were assessed in relation to MFI scores using linear regression in 3 sequential, additive models with model-fit comparisons.

Results: 692 people with 9 different forms of vasculitis completed the IPQ-R.  Disease status characteristics included current disease remission (45%), severe disease manifestation (54%), median disease duration (7.4 years), and remission duration ≥ 1 year (27%). Mean MFI score was 15.0 (±3.9). Disease activity, remission duration, age, race, depression, sleep disturbance, and all IPQ-R dimensions except timeline were significantly associated with MFI scores (Table). Sequential models demonstrated that IPQ-R dimensions explained an additional 18% of variability in fatigue scores after accounting for disease status and clinical variables. 56% of variability in fatigue scores remained unexplained in the full model.

Conclusion: Patient-reported measures of disease activity and remission duration are associated with fatigue, suggesting that patients consider fatigue a manifestation of active vasculitis. Illness perceptions significantly explain differences in fatigue scores beyond what can be explained by measures of disease status and depression. These data suggest that in vasculitis i) fatigue is a major domain of illness only partially related to disease activity as currently assessed; ii) illness perceptions may have a causal role in fatigue; and iii) the mechanisms underlying fatigue are complex and multifactorial. These findings have important implications for the incorporation of fatigue measures into overall outcome assessment in vasculitis.