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Fatigue: The “Invisible Disease” in RA

Fatigue: The “Invisible Disease” in RA

How many of your rheumatoid arthritis (RA) patients are burdened by fatigue? Probably almost all of them, and it may have an impact on remission that you don't realize.

A few recent findings on the subject:

Eight of ten people with RA have chronic fatigue that has more impact on their daily life than pain.1,2 Biologics seem to have no significant effect on this fatigue; its relationship to inflammation is unclear at best.3 Almost half of patients in the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study report moderate to high levels of fatigue and pain despite minimal inflammation.4

Described in ways similar to cancer fatigue, it remains poorly defined. Based on the Piper Fatigue Scale for cancer patients, RA fatigue is described as  "unpleasant, unusual, abnormal or excessive whole-body tiredness," unrelated to activity or exertion, lasting more than a month, not easily dispelled by sleep or rest. Lacking a standardized, validated definition and assessment scale keeps the chronic fatigue of RA largely an “invisible disease,” says Britain’s National Rheumatoid Arthritis Society (NRAS),2 stressing that itis distinct from Chronic Fatigue Syndrome,  which has its own criteria.

Several good tools exist to measure RA fatigue, which may be useful clinically. At the urging of patients, in 2006 the international Outcome Measures in Rheumatology (OMERACT) organization added fatigue to its “core set” of RA criteria that should be measured in randomized clinical trials.5 OMERACT has rated  the first two of the following as reliable for assessing fatigue in RA:

•   The Multi-Dimensional Assessment of Fatigue (MAF) questionnaire. Available after free registration at www.son.washington.edu/research/maf/, it includes 16 questions covering four dimensions of fatigue: severity, distress, and interference in activities of daily living, along with frequency and change in fatigue during the previous week. in a global fatigue index ranging from 0, “no fatigue” to 50, “severe fatigue.” A 2011 review in Arthritis Care & Research of more than a dozen patient-reported outcome scales saic the MAF “might be useful in clinical practice in providing a global score, while the multiple questions might help identify target areas for therapeutic intervention.”6

•   The Functional Assessment Chronic Illness Therapy (Fatigue) (FACIT-F) scale. Developed for cancer patients, but OMERACT says it passes muster for reliability in RA.

•  The Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF MDQ) created after the OMERACT assessment, may "inform individualized self-management interventions," according to the authors of the 2011 review (see MAF, above).6 The 20-item paper-and-pencil BRAF MDQ covers four domains of fatigue:

-- physical (e.g., average fatigue level over last 7 days)
-- functional (e.g., “has fatigue made it difficult to bathe or shower?”)
-- cognitive (e.g., "has fatigue made it difficult to concentrate?")
-- and emotional (e.g., “has being fatigued upset you?”).

OMERACT says any such fatigue measurement tools (including the widely used VAS (visual assessment scale) would need to be refined before being used to support recommended changes in RA treatment.5

Patients in remission may still have fatigue. ACR criteria for RA remission include "absence of fatigue," but a new study shows that measuring remission by other standards may overlook fatigue. Among an observational cohort of 428 RA patients (two-thirds of them women around age 50 who’d had RA for more than a decade), patients classed in remission by the 28-joint count Disease Activity Score-erythrocyte sedimentation rate (DAS28-ESR) or the Simplified Disease Activity Index (SDAI) were more likely to still have fatigue (as measured by MAF) than those fulfilling 2011 remission criteria of the ACR and and the European League Against Rheumatism (EULAR) .7

Biologics may relieve fatigue, but only temporarily. A study that tracked fatigue in 125 Irish patients with active inflammatory arthritis found that tumor necrosis factor (TNF) blockers improved fatigue by around 35% over the first three months. But treatment did not produce additional benefits after that, suggesting that fatigue seems to relate to “a variety of biobehavioral variables ... such as cognitive, behavioral and personal factors.”

Cognitive behavior therapy (CBT) may help. CBT uses cognitive “reframing” to change patterns of thinking and behaviors. A randomized clinical trial at the University of the West of England in Bristol showed that compared to mere education about fatigue in RA, a 13-session CBT program reduced fatigue and improve RA patients’ ability to cope.8

Among 127 patients who had severe fatigue and limited ability to cope, despite low levels of pain and disease activity at baseline, MAF scores  dropped from 30.99 at baseline to 23.99 after 18 weeks among the CBT group,but less than two points, from 30.46 to 28.99, in the education group.8 The CBT group also had significantly lower VAS scores as well as less disability, depression, helplessness, self-efficacy, and better sleep.

Overlook RA fatigue at your (patient's) peril. “Concentrating on improving fatigue self-management," the researchers conclude, "may lead to improvement in well-being.”8 On the other hand, warn the authors who analyzed fatigue as a factor in remission, ignoring it may run the risk of improperly targeting treatment.7





1.   Repping-Wuts H, Van Riel P, Van Achterberg T. Editorial: Fatigue in patients with rheumatoid arthritis: what is known and what is needed? Rheumatology (2009) 48:207-209 doi:10.1093/rheumatology/ken399.

2.  Invisible Disease: Rheumatoid Arthritis and Chronic Fatigue. Survey 2014. The National Rheumatoid Arthritis Society (UK). Accessed August 1 2014 from: www.nras.org.uk.  

3.  Minnock P, McKee G, Bresnihan B, et al. How much is Fatigue Explained by Standard Clinical Characteristics of Disease Activity in Patients with Inflammatory Arthritis: A Longitudinal Study. Arthritis Care & Research (2014) doi: 10.1002/acr.22387Accepted MS.

4.  Lee YC, Frits ML, Iannaccone CK, et al. Subgrouping of Patients With Rheumatoid Arthritis Based on Pain, Fatigue, Inflammation, and Psychosocial Factors. Arthritis & Rheumatology (2014) 66:2006–2014, August 2014. doi: 10.1002/art.38682.

5.  Kirwan JR, Minnock P, Adebajo A, et al., Patient Perspective: Fatigue as a Recommended Patient Centered Outcome Measure in Rheumatoid Arthritis. J Rheum. (2007) 34:1174-1177.

6.  Hewlett S, Dures E, Aleida C. Measures of Fatigue: Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF MDQ), Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scales (BRAF NRS) for Severity, Effect, and Coping, Chalder Fatigue Questionnaire (CFQ), Checklist Individual Strength (CIS20R and CIS8R), Fatigue Severity Scale (FSS), Functional Assessment Chronic Illness Therapy (Fatigue) (FACIT-F), Multi-Dimensional Assessment of Fatigue (MAF), Multi-Dimensional Fatigue Inventory (MFI), Pediatric Quality Of Life (PedsQL) Multi-Dimensional Fatigue Scale, Profile of Fatigue (ProF), Short Form 36 Vitality Subscale (SF-36 VT), and Visual Analog Scales (VAS). Arthritis Care & Research. (2011) 63(S11):S263–S286. doi:10.1002/acr.20579.

7.  Inanc N, Yilmaz-Oner S, Can M, et al. The Role of Depression, Anxiety, Fatigue, and Fibromyalgia on the Evaluation of the Remission Status in Patients with Rheumatoid Arthritis. J Rheumatol. (2014) Aug 1. pii: jrheum.131171. [Epub ahead of print].

8.  Hewlett S, Nick Ambler N, Almeida C, et al., Self-management of fatigue in rheumatoid arthritis: a randomised controlled trial of group cognitive-behavioural therapy. Ann Rheum Dis (2011) 70:1060–1067. doi 10.1136/ard.2010.144691.

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