Correlation of Fatigue with Clinical Parameters and Quality of Life in Rheumatoid Arthritis
Yasemin Turan1, Zehra Kocaağa2, Hikmet Koçyiğit2, Alev Gürgan2, Korhan Barış Bayram2, Serdar İpek2
1Adnan Menderes Üniversitesi Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı, Aydın, Turkey
2Atatürk Eğitim ve Araştırma Hastanesi, Fiziksel Tıp ve Rehabilitasyon Kliniği, İzmir, Turkey
Keywords: Rheumatoid arthritis, disease activity, fatigue, quality of life, radiological involvement
Objective: We aimed to investigate fatigue and its relationship with disease activity, radiological findings and quality of life in patients with rheumatoid arthritis (RA).
Materials and Methods: 41 patients who were diagnosed as RA according to criteria of ACR and 38 healthy controls were enrolled to this study. Patients were asked to record the severity of rest pain (Visual Analog Scale) and duration of morning stiffness. Fatigue was evaluated by the Multidimensional Assessment of Fatigue (MAF) test. Disease activity and quality of life were assessed respectively with DAS-28 and Short Form-36 (SF-36). Radiologic involvement was evaluated according to modified Larsen's grading system.
Results: The mean age of patient and control groups were 50.9±13.4 years and 50±10.1 years, respectively. Two groups were similar with respect age (p=0.744). The median MAF total score was higher in patients with RA (38.5, min-max: 4-50) than in control subjects (22.5, min-max: 0-42) (p<0.001). There were significant correlations between MAF and DAS-28 scores (r=0.478, p=0.004), rest pain (r=0.491, p=0.001), ACR functional scale (r=0.563, p<0.001) and four dimensions of SF36; physical role (r=-0.504, p=0.014), bodily pain (r=-0.416, p=0.048), vitality (r=-0.522, p=0.011), emotional role (r=-0.523, p=0.011).
Conclusion: Fatigue symptom may be quite disabling for patients with rheumatoid arthritis. It is affected by disease activity and pain but not by disease duration and radiologic score. Therefore, it is concluded that fatigue is essentially related with disease activity rather than the chronic inflammatory process in RA. (Turk J Rheumatol 2010; 25: 63-7)
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting primarily the joints and causing pain, deformity, joint destruction and disability . The impacts of RA include systemic features such as fatigue, weight loss and increased mortality .
Fatigue is a common and quite important symptom in patients with RA [3,6]. It's prevalence in RA has been found to be 80-93% [5,8]. Although it is so common, it is not investigated in the routine follow-up of RA patients [3,18]. Excessive fatigue may lead to a reduction in both the quality and quantity of work output . No research has been found in the literature regarding the relationship of fatigue with quality of life and radiologic involvement in patients with rheumatoid arthritis.
The aim of this study was to determine the severity of fatigue in RA and its relationship with disease activity, quality of life, clinical, radiological and functional parameters.
Patients and Methods
Forty-one patients who were diagnosed as RA according to the criteria of American College of Rheumatology (ACR)  and 38 healthy subjects were included in this study. Patients with malignancy, fibromyalgia syndrome, other systemic inflammatory rheumatic diseases and psychiatric disorders were excluded.
Demographic data and treatment history were recorded in all cases. A 100 mm visual analogue scale (VAS) was used to determine the pain intensity at rest and during activity. Duration of morning stiffness (minute), presence of night pain and disease duration (month) were noted. Disease activity score (DAS) for 28-joint counts and its constituent components 28 tender joint count, 28 swollen joint count, patient's global assessment were recorded .
The Multidimensional Assessment of Fatigue (MAF) scale contains 16 items and measures five dimensions of fatigue: namely, severity, distress, impact on activities of daily living and timing. Each 100 mm VAS was changed to a 10-point numerical rating scale. Scores ranged from 0 (no fatigue) to 50 (severe fatigue) .
Radiographs of the hand and foot were assessed by the same physician (YT). 44 joints were evaluated: 10 metacarpophalangeal, 10 metatarsophalangeal, 18 proximal interphalangeal, 4 interphalangeal of the thumbs, 2 wrist and 2 ankle joints. Each joint was graded on a 0-5 point scale (0, normal condition; 1, slight abnormality; 2, definite abnormality; 3, marked abnormality; 4, severe abnormality; 5, mutilating abnormality) according to Larsen . Laboratory investigation included erythrocyte sedimentation rate (ESR) (using the standard Westergren method), serum C-reactive protein (CRP) (using the nephelometer assay), total blood count and rheumatoid factor measurements.
Functional status of RA patients was evaluated according to the ACR functional classification. According to this stage 1: patient can function normally, stage 2: patient can work and perform his or her daily activities with minor limitations, stage 3: patient can take care of him or herself but has major limitations, stage 4: patient is totally dependent .
The Medical Outcomes Study Short Form 36 (SF-36) was used to assess health-related quality of life. The SF-36 is a widely applied generic instrument for measuring health status, and consists of 8 domains: physical functioning, social functioning, physical role, emotional role, mental health, vitality, bodily pain, and general health perception. Scores range from 0 (worst) to 100 (best) with higher scores indicating better health status [22,23].
Statistical analyses were performed by using the software Statistical Package Sciences (SPSS) for Windows version 11.0. For the discrepancies among the groups, Mann-Whitney U test and student's t test were used. Spearman's correlation coefficient was used to assess relationship between fatigue and clinical parameters. Significance level was 0.05.
The mean age of patient and control groups were 50.9±13.4 years and 50±10.1 years, respectively. Two groups were similar with respect to age (p=0.744). The median MAF total score was higher in patients with RA (38.5, min-max: 4-50) than in control subjects (22.5, min-max: 0-42) (p<0.001). The demographic and clinical characteristics of patients and control subjects are shown in Table 1. Components of MAF (degree, severity, distress, impact and timing) are shown in Table 2.
There were significant correlations between MAF and DAS-28 scores (r=0.478, p=0.004), rest pain (r=0.491, p= 0.001) and ACR functional scale (r=0.494, p=0.001). There was a significant negative correlation between MAF and four dimensions of SF36; physical role (r= -0.504, p=0.014), bodily pain (r=-0.416, p=0.048), vitality (r=-0.522, p=0.011), and emotional role (r=-0.523, p=0.011). No significant relationship was found between MAF and disease duration, morning stiffness, Larsen score, ESR, CRP and hemoglobin levels (p>0.05) (Table 3).
Fatigue, has been reported as an important symptom in RA and appears to be multifactorial and multidimensional [3,6]. Currently, MAF is used to determine various characteristics of the fatigue symptom in RA patients. Since MAF is short and easy to complete, it can be used in clinical practice for multiple purposes including assessment of baseline reports of fatigue.
In our study, the mean MAF total score was higher in patients with RA than in control subjects. Additionally, sub scores of the MAF were higher in RA patients. Similarly, Belza et al.  and Mancuso et al.  reported that fatigue scores were significantly higher in persons with RA compared to healthy controls.
We found that the total scores of MAF were significantly correlated with the DAS-28 scores which is in accordance with the results obtained by Pollard et al. . In contrast to these studies, Huyser et al.  did not find a correlation between fatigue and disease activity. A former study however, emphasized that lack of fatigue was a feature of clinical remission in RA .
Pain is a major problem experienced by patients with RA and affects mobility and quality of life . In concordance with the results of other studies, we demonstrated a significant correlation between fatigue and pain [5,9,10,12,14]. Pain is one of the most important symptoms that increase during the active phase of RA . We can conclude that increased pain in patients with higher disease activity is accompanied by a more severe fatigue.
A relationship was shown between the MAF and ACR functional scale scores in our study. Several authors have investigated functional status and fatigue and found a significant correlation between them [4,7,10]. Studies investigating the relationship between fatigue and quality of life in RA have contradictory results [9,12]. Vitality and mental health which are subgroups of SF 36 have been found significantly correlated with fatigue . Wolfe et al. , did not demonstrate a significant relationship between the MAF scores, vitality and physical function. However in our study, we found a correlation between MAF and four dimensions of SF36.
No significant relationship was found between the MAF scores, disease duration and Larsen scores. Belza et al. , have also reported that no significant correlation exists between the severity of fatigue and disease duration. In contrast to these, Riemsma et al. , have found a significant relationship between fatigue and disease duration. No research has been conducted so far that aims to investigate the relationship of radiologic involvement with fatigue. Radiological findings become more prominent as the disease acquires chronicity . Since we did not find any correlation between fatigue and disease duration, it may not be surprising to determine the lack of relationship between the radiologic involvement and fatigue.
In our study, laboratory measurements like ESR, CRP and hemoglobin levels were found to be not related to fatigue. Riemsma et al. , found similar results for ESR and hemoglobin levels. Belza et al. , have reported that fatigue and CRP are not related. Both CRP and ESR are nonspecific markers of inflammation that correlate with disease activity , as well as being sensitive measures of change in response to treatment in clinical trials .
Morning stiffness is caused by edema of the synovium and periarticular tissues in inflammatory conditions. It is most pronounced after sleep, due to redistribution of interstitial fluid during sleep . There were no correlation between MAF total scores and morning stiffness in our study. In accordance with this finding, Pollard et al. , reported no relationship between fatigue and morning stiffness.
In conclusion, fatigue as a major symptom in RA patients, needs to be measured properly with respect to its intensity by appropriate measures, such as MAF. The MAF provides more insight into specific dimensions of fatigue. Fatigue becomes more prominent as disease activity increases which seems to be independent of the disease duration. Quality of life is affected negatively by fatigue in patients with rheumatoid arthritis.
Conflict of Interest
No conflict of interest is declared by authors.
- Harris ED. Clinical features of rheumatoid arthritis. In: Ruddy S, Harris E. D, Sledge CB, eds. Kelley's Textbook of Rheumatology. 6th edition, Elsevier, Philadelphia: WB. Saunders Company; 2001; 967-1000.
- Gabriel SE, Crowson CS, Kremers HM, Doran MF, Turesson C, O\'Fallon WM, et al. Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum 2003; 48: 54S-58S.
- Tack B. Self-reported fatigue in rheumatoid arthritis: a pilot study. Arthritis Care Res 1990; 3: 154-7.
- Tack B. Fatigue in rheumatoid arthritis: conditions, strategies, and consequences. Arthritis Care Res 1990; 3: 65-70.
- Belza BL. Comparison of self-reported fatigue in rheumatoid arthritis and controls. J Rheumatol 1995; 22: 639-43.
- Repping-Wuts H, Fransen J, van Achterberg T, Bleijenberg G, van Riel P. Persistent severe fatigue in patients with rheumatoid arthritis. J Clin Nurs 2007; 16: 377-83.
- Pinals R, Masi AT, Larsen RA. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 1981; 24: 1308-15.
- Belza B, Henke C, Yelin E, Epstein WV, Gilliss CL. Correlates of fatigue in older adults with rheumatoid arthritis. Nurs Res 1993; 42: 93-9.
- Pollard LC, Choy EH, Gonzalez J, Khoshaba B, Scott DL. Fatigue in rheumatoid arthritis reflects pain, not disease activity. Rheumatology (Oxford) 2006; 45: 885-9.
- Crosby LJ. Factors which contribute to fatigue associated with rheumatoid arthritis. J Adv Nurs 1991; 16: 974-81.
- Huyser BA, Parker JC, Thoreson R, Smarr KL, Johnson JC, Hoffman R. Predictors of subjective fatigue among individuals with rheumatoid arthritis. Arthritis Rheum 1998; 41: 2230-7.
- Wolfe F. Fatigue assessments in rheumatoid arthritis: comparative performance of visual analog scales and longer fatigue questionnaires in 7760 patients. J Rheumatol 2004; 31: 1896-902.
- Riemsma RP, Rasker JJ, Taal E, Griep EN, Wouters JM, Wiegman O. Fatigue in rheumatoid arthritis: the role of self-efficacy and problematic social support. Br J Rheumatol 1998; 37: 1042-6.
- Mancuso CA, Rincon M, Sayles W, Paget SA. Psychosocial variables and fatigue: a longitudinal study comparing individuals with rheumatoid arthritis and healthy controls. J Rheumatol 2006; 33: 1496-502.
- Zautra AJ, Fasman R, Parish BP, Davis MC. Daily fatigue in women with osteoarthritis, rheumatoid arthritis, and fibromyalgia. Pain 2007; 128: 128-35.
- Rupp I, Boshuizen HC, Jacobi CE, Dinant HJ, van den Bos GA. Impact of fatigue on health-related quality of life in rheumatoid arthritis. Arthritis Rheum 2004; 51: 578-85.
- Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI): psychometric qualities of an instrument to assess fatigue. J Psychosom Res 1995; 39: 315-25.
- Hewlett S, Cockshott Z, Byron M, Kitchen K, Tipler S, Pope D et al. Patients\' perceptions of fatigue in rheumatoid arthritis: overwhelming, uncontrollable, ignored. Arthritis Rheum 2005; 53: 697-702.
- Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315-24.
- Smolen JS, Breedveld FC, Schiff MH, Kalden JR, Emery P, Eberl G, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology 2003; 42: 244-57.
- Van Der Heijde DM. Plain X-ray in rheumatoid arthritis: overview of scoring methods, their reliability and applicability. Clin Rheumatol 1996; 435-53.
- Ware JE, Jr, SF-36 Health Survey Update. Spine 2000; 25: 3130-9.
- Koçyiğit H, Aydemir Ö, Fişek G, Ölmez N, Memiş A. Kısa Form-36 (KF-36)'nın Türkçe versiyonunun güvenilirliği ve geçerliliği: Romatizmal hastalığı olan bir grup hasta ile çalışma. İlaç ve Tedavi Dergisi 1999; 12: 102-6.
- Ying KN, While A. Pain relief in osteoarthritis and rheumatoid arthritis: TENS. Br J Community Nurs 2007; 12: 364-71.
- Vlaar AP, Ten Klooster PM, Taal E, Gheith RE, El-Garf AK, Rasker JJ, et al. A cross-cultural study of pain intensity in Egyptian and Dutch women with rheumatoid arthritis. J Pain 2007; 8: 730-6.
- Kirvan JR. Links between radiological change, disability, and pathology in rheumatoid arthritis. J Rheumatol 2001; 28: 881-6.
- Van der Heijde DM, Van't Hof M, van Riel PL, van Leeuwen MA, van Rijswijk MH,van de Putte LB. Validity of single variables and indices to measure disease activity in rheumatoid arthritis. Ann Rheum Dis 1992; 51: 177-81.
- Anderson JJ, Chernoff MC. Sensitivity to change of rheumatoid arthritis clinical trial outcome measures. J Rheumatol 1993; 20: 535-7.
- Fuchs AH, Sergent JS. Rheumatoid Arthritis: The Clinical Picture In: Koopman WJ (Ed). Arthritis and Allied Conditions. A Textbook of Rheumatology. Baltimore: Williams & Wilkins, 1997; 1041-70.