Devastating Impact Of Rheumatoid Arthritis Fatigue
Overview
Fatigue is a prevalent symptom that significantly impacts the outcomes and functioning of individuals with rheumatoid arthritis (RA). This study aimed to evaluate fatigue in RA patients using two different scales, while also validating their consistency and thoroughly examining the fatigue-related risk factors.
In this case-control study, fatigue levels in 160 RA patients and 60 healthy controls were measured using the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) and the Chinese version of the Brief Fatigue Inventory (BFI-C). The disease activity in RA patients was assessed using the 28-joint disease activity score based on erythrocyte sedimentation rate.
Rheumatoid arthritis patients exhibited significantly higher fatigue levels on both the BRAF-MDQ and BFI-C scales compared to healthy controls (all p < .001). There was a strong positive correlation between the global fatigue scores of the BRAF-MDQ and BFI-C in both rheumatoid arthritis patients (r = .669, p < .001) and healthy controls (r = .527, p < .001). Moreover, Kendall’s tau-b test demonstrated a high level of consistency between the global fatigue scores of the two scales for both RA patients (W = 0.759, p < .001) and healthy controls (W = 0.933, p < .001). Notably, a higher education level was independently associated with lower BRAF-MDQ global fatigue scores (B = −4.547; 95% confidence interval: −7.065, −2.029; p < .001) and BFI-C global fatigue scores (B = −0.613; 95% confidence interval: −0.956, −0.269; p = .001). Conversely, higher swollen joint counts (B = 1.965; 95% confidence interval: 1.375, 2.554; p < .001) and clinical disease activity index (B = 0.053; 95% confidence interval: 0.005, 0.102; p = .032) were independently linked to higher fatigue scores on the respective scales.
Fatigue is a common and significant issue for rheumatoid arthritis patients, with independent associations found with education level and disease activity. The BRAF-MDQ and BFI-C scales showed a high degree of consistency in measuring fatigue, making them reliable tools for assessing this symptom in rheumatoid arthritis patients.
Introduction
Fatigue is a pervasive and debilitating symptom commonly experienced by individuals with rheumatoid arthritis (RA). While inflammation plays a role, fatigue in RA is more likely influenced by behavioral and psychological factors rather than direct disease mechanisms. Unlike typical fatigue, the exhaustion associated with rheumatoid arthritis is not alleviated by rest, significantly impacting patients’ quality of life and creating challenges across various aspects of their lives, including mental health, physical well-being, work, and social interactions. This underscores the importance of investigating fatigue and its associated risk factors to better manage this symptom and improve outcomes for rheumatoid arthritis patients.
Previous research has identified several risk factors linked to fatigue in rheumatoid arthritis, including disease activity, education level, age, disease duration, functional disability, and quality of life. Additionally, mental health, pain, sleep disorders, and comorbid conditions like hypertension, hypothyroidism, and anemia have also been associated with fatigue in rheumatoid arthritis. Seasonal variations, particularly increased fatigue during winter, have also been reported. However, these studies often rely on a single scale for evaluating fatigue, and few have examined the consistency among different assessment tools.
The Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) is a specialized tool developed in collaboration with RA patients, offering a comprehensive evaluation by measuring fatigue across four dimensions from the patient’s perspective. This tool has gained widespread use in clinical research globally. Another tool, the Brief Fatigue Inventory (BFI), is known for its simplicity and ease of use. The Chinese version of the BFI (BFI-C) has been validated as a reliable instrument for assessing fatigue in Chinese RA patients. Given the strengths of the BRAF-MDQ and BFI-C, this study employed both scales to assess fatigue in rheumatoid arthritis patients and aimed to validate their consistency.
This study not only used the BRAF-MDQ and BFI-C to provide a thorough assessment of fatigue but also aimed to evaluate the consistency between these tools. Additionally, the study sought to identify the risk factors contributing to fatigue in rheumatoid arthritis patients, with the goal of applying these findings to clinical practice for better fatigue management.
Method
Between December 2022 and February 2023, a case–control study was conducted involving 160 patients diagnosed with rheumatoid arthritis (RA) at the Affiliated Suqian First People’s Hospital of Nanjing Medical University. The study participants met the following criteria: (i) RA diagnosis based on the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism criteria; (ii) aged 18 years or older; and (iii) voluntarily consented to participate. Patients were excluded if they had a history of malignancies, psychiatric or neurological conditions, or major surgeries, or if they exhibited moderate-to-severe cognitive impairment that could hinder questionnaire completion. Additionally, 60 healthy individuals were recruited as controls, selected based on normal physical and biochemical examination results, absence of significant medical history, and their ability to complete the questionnaires.
The study was approved by the Ethics Committee of the Affiliated Suqian First People’s Hospital of Nanjing Medical University (approval number: 20230005).
Clinical data for RA patients included demographics (age, gender, BMI, education level, marital and employment status, and location), disease history (hypertension, hyperlipidemia, diabetes), disease characteristics (disease duration, rheumatoid factor and anticitrullinated protein autoantibody status, tender and swollen joint counts, erythrocyte sedimentation rate, C-reactive protein levels, DAS28 ESR score, patient’s and physician’s global assessment scores, and clinical disease activity index), and treatment details.
Fatigue levels in both RA patients and healthy controls were assessed using the BRAF-MDQ and BFI-C questionnaires. The BRAF-MDQ, comprising 20 items, provides a global fatigue score and scores for physical, living, cognitive, and emotional domains. Higher scores indicate more severe fatigue. The BFI-C evaluates fatigue severity and interference, with a global score reflecting overall fatigue level. Functional disability and quality of life for RA patients were measured using the Health Assessment Questionnaire Disability Index (HAQ) and the Short-Form Health Survey (SF-12), respectively.
Statistical analyses were performed using SPSS v22.0 and GraphPad Prism v7.0. Group comparisons were conducted using t-tests, while Pearson and Spearman correlation tests assessed relationships between variables. Kendall’s tau-b test evaluated consistency, with a coefficient (W) > 0.7 indicating good consistency. Linear regression was applied to identify factors associated with fatigue, with significance set at p < .05.
Result
In a comparative study of rheumatoid arthritis (RA) patients and healthy controls, notable differences were observed in demographic and clinical characteristics, as well as fatigue levels. The RA cohort had a mean age of 57.9 years with a gender distribution of 27.5% males and 72.5% females. The healthy control group, on the other hand, had a mean age of 48.5 years, with 36.7% males and 63.3% females. The age difference between the two groups was statistically significant (p < .001), indicating that RA patients were older on average compared to the healthy controls. Additionally, there was a significant difference in educational attainment between the RA patients and the healthy controls (p = .005), suggesting that education level may vary between these groups. However, no significant differences were found in gender distribution (p = .186) or body mass index (BMI) (p = .146) between the RA patients and healthy controls.
Fatigue, a common and debilitating symptom of RA, was assessed using the BRAF‐MDQ and BFI‐C scales. RA patients exhibited significantly higher levels of fatigue compared to healthy controls across all measured domains. The BRAF‐MDQ results revealed increased global fatigue in RA patients, with elevated scores in physical fatigue (p < .001), living fatigue (p < .001), cognitive fatigue (p < .001), and emotional fatigue (p < .001). Similarly, the BFI‐C scores showed that RA patients experienced higher global fatigue (p < .001), fatigue severity (p < .001), and fatigue interference (p < .001) compared to healthy controls. This indicates that RA patients experience a broader and more intense impact of fatigue.
The study also explored factors associated with fatigue in RA patients. Univariate linear regression analysis indicated that higher education levels were associated with lower global fatigue scores on both the BRAF‐MDQ and BFI‐C. This suggests that better educational attainment may be linked to reduced fatigue levels. Conversely, higher swollen joint count (SJC) and clinical disease activity index (CDAI) scores were associated with increased global fatigue scores. Multivariate linear regression analysis confirmed these findings, showing that higher education was independently associated with lower global fatigue scores (B = −4.547, p < .001 for BRAF‐MDQ; B = −0.613, p = .001 for BFI‐C), while SJC and CDAI scores were independently linked to higher global fatigue scores (B = 1.965, p < .001 for BRAF‐MDQ; B = 0.053, p = .032 for BFI‐C).
Regarding the impact of methotrexate, a common treatment for RA, the study found no significant differences in fatigue scores between patients treated with methotrexate and those who were not (all p > .05). This suggests that methotrexate treatment does not significantly alter fatigue levels as measured by either the BRAF‐MDQ or BFI‐C.
Further analysis revealed that education level had an inverse correlation with SJC (r = −0.339, p < .001), indicating that higher education may be associated with fewer swollen joints. However, no significant correlation was found between education level and CDAI score (r = −0.056, p = .480). In RA patients with high SJC (>3.0), education level did not significantly influence fatigue scores. However, in patients with high CDAI (>18.0), higher education was associated with lower fatigue scores on both BRAF‐MDQ and BFI‐C (all p < .05).
In the healthy control group, education level was inversely correlated with physical fatigue on the BRAF‐MDQ (p = .001), though it was not related to other fatigue domains or BFI‐C scores (all p > .05). Higher education levels did not show a significant correlation with BRAF‐MDQ or BFI‐C scores in healthy controls (all p > .05).
Lastly, the study assessed the consistency between the BRAF‐MDQ and BFI‐C fatigue measures. A strong positive correlation was found between the global fatigue scores of these two scales for both RA patients (r = .669, p < .001) and healthy controls (r = .527, p < .001). The consistency between the scales was high, with Kendall’s tau‐b test showing a significant alignment in RA patients (W = 0.759, p < .001) and healthy controls (W = 0.933, p < .001). This indicates that the BRAF‐MDQ and BFI‐C scales are consistent in their assessment of fatigue across both RA patients and healthy controls.
Conclusion
The study revealed several key findings regarding fatigue in rheumatoid arthritis (RA) patients:
RA patients exhibited higher levels of fatigue across multiple dimensions, as assessed by both the BRAF-MDQ and BFI-C scales. This included global fatigue, physical fatigue, and emotional fatigue, compared to healthy controls.
The analysis identified higher education levels and disease activity (measured by the Simple Joint Count (SJC) and Clinical Disease Activity Index (CDAI)) as independent factors associated with increased fatigue. Specifically, higher education was linked with greater fatigue as measured by BRAF-MDQ and BFI-C scores.
Both the BRAF-MDQ and BFI-C scales showed a high level of consistency in measuring fatigue, indicating that these tools are comparable in assessing fatigue levels in RA patients. Fatigue in RA patients is influenced by a range of factors including inflammation, pain, medication effects, cognitive and behavioral aspects, and personal circumstances such as responsibilities and social support. Although the precise mechanisms remain unclear, these factors collectively contribute to the fatigue experienced by RA patients. The study found that higher education levels and greater disease activity were associated with increased fatigue, suggesting that education might improve disease understanding and support, while high disease activity exacerbates fatigue due to greater joint pain and inflammation.
The study found no specific medical treatment or drug regimen was independently linked with fatigue reduction. This aligns with previous research indicating that different medications do not significantly affect fatigue levels in RA patients.
Both BRAF-MDQ and BFI-C scales are effective for evaluating fatigue in RA patients, with the BFI-C scale being a convenient alternative due to its ease of use.
The study faced limitations such as a mismatch in sample sizes between RA patients and healthy controls, a need for a larger sample size for more definitive conclusions, and the cross-sectional nature of the study. Additionally, the research was conducted at a single center in China, which may affect the generalizability of the findings.
Fatigue is prevalent among RA patients, with education level and disease activity being significant risk factors. The choice of assessment tool (BRAF-MDQ vs. BFI-C) does not significantly impact the measurement of fatigue, suggesting interchangeability between these scales. Further research with larger, longitudinal studies is needed to better understand and manage fatigue in RA patients.
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