Monday, March 25, 2013

Fatigue and Rheumatoid Arthritis

During the past months it seend that nearly every patient complained about fatigue and flare or remission weren't good predictors. I've already written a blogpost on fatigue, link: And fatigue is different from morning stiffness, another common symptom.

Recently I've read the following tweet on Twitter:
AmerCollRheumatology @ACRheum The Puzzle of Fatigue in #Rheumatoid Arthritis #rheumatology

Fatigue has been indexed for about 25 abstracts presented at the ACR 2012 in Washington. Quite a lot of studies can't be applied to patients with rheumatoid arthritis, but a lot of these studies are relevant. So the tweet and the article by Mary Beth Nierengarten prompted me to look again into the abstracts and fatigue in general.

R. Alten and colleagues presented: "Improved Fatigue-Related Quality of Life in CAPRA-2, a 12 Week Study of 5-Mg Modified (Delayed) Release Prednisone in Rheumatoid" (Abstract No. 367). If fatigue is associated with inflammation it isn't farfetched to expect fatigue getting better under prednisone.

J. P. Hampson and colleagues presented: "Frontal Brain Connectivity to the Default Mode Network Is Associated with Subjective Fatigue Irrespective of Pain and Depression" Abstract No. 803). They tested fibromyalgia patients, but maybe some of the results might also apply to patients with rheumatoid arthritis. They concluded: "This study suggests that connectivity of multiple brain regions to the DMN is associated with subjective reports of fatigue."

S. van Dartel and colleagues presented: "Association of Actometer Assessed Physical Activity and Fatigue in Patients with Rheumatoid Arthritis: Patients with a Lower Daily Activity Have More Fatigue" (Abstract No. 1232). They concluded: "In RA, a higher level of physical activity was associated with less fatigue."

H. Lööf and colleagues presented: "Pain and Fatigue in Adult Patients with Rheumatoid Arthritis - Associations with Demographic Factors, Disease Related Factors, Body Awareness, Emotional and Psychosocial Factors" (Abstract No. 1571). They concluded: "This study identifies that in patients with Rheumatoid arthritis fatigue and pain appears to be associated with disease related factors. Furthermore, fatigue was related to body awareness and emotional factors."

I've already quoted the study of B. I. Bremander and colleagues: "Smoking Is Associated with Worse and More Widespread Pain, Worse Fatigue, General Health and Quality of Life in a Swedish Population Based Cohort of Patients with Psoriatic Arthritis" (Abstract No. 1828). If smoking worsens fatigue in patients with psoriatic arthritis it's only a matter of time to show that smoking also worsens fatigue in patients with rheumatoid arthritis.

N. Lukkahatai and colleagues looked at: "Genomic Categories of Fatigue in Women with Fibromyalgia" (Abstract 1874). They concluded: "Within FM women with high fatigue, there appears to be two distinct patterns of gene expression. These genomic patterns correspond with differences in behavioral characteristics." Though this study is on patients with fibromyalgie, I doubt that one won't find corresponding genomic patterns in patients with rheumatoid arthritis.

P. P. Katz and colleagues presented: "Obesity Is Associated with Higher Levels of Fatigue in RA" (Abstract No. 2411). They concluded: " Obesity appears to play a role in RA fatigue, even after controlling for important covariates such as disease activity, sleep, and depression."

K. Loeppenthin and collegues presented: "Quality of Sleep, Physical Activity and Fatigue in Patients with Rheumatoid Arthritis. A Cross-Sectional Study" (Abstract No. 2689). They concluded: "A high prevalence of sleep disturbances was observed. This study indicates that PA and fatigue play a significant role in self-reported sleep quality." Very intersting, as these findings show parallels to fibromyalgia.

In her article Mary Beth Nierengarten cited R. Geenen from Utrecht University in the Netherlands: “Fatigue is much more strongly correlated with cognitive variables, such as helplessness and catastrophizing thoughts, and behavioral variables, such as pacing of activities, physical fitness, and patterns of sleep and awakening”. So it might well be that we'll reach a better understanding of what has often been called fibromyalgianess in rheumatoid arthritis patients, "the precise physiological substrate of fatigue remains largely unknown". Inflammatory parameters only show a low correlation to fatigue.

We still lack established instruments for monitoring fatigue. There are some being used in research, but they aren't in current every day practice use. So using a VAS or NRS scale concerning fatigue at every visit would already give an overview until better tools are developed. Ch. Bode from the University of Twente in the Netherlands, "reviewed a number of novel measurements of fatigue that can be useful in helping to tailor intervention strategies". There's a table of possible tools, which are interesting for research, but aren't useful in daily practice as rheumatologist won't have the time to read and evaluate diaries. For research however these tools are relevant.

S. Hewlett of the University of the West of England, looked at nonpharmacological interventions of fatigue in rheumatoid arthritis patients. Cognitive behavioral therapy, low-impact aerobic exercise, pool therapy and others showed efficacy. At our center, we use low-impact aerobic exercise and pool therapy as a routine measure. We have a clinical psychologist, who is called, when the patient agrees, though we don't initiate cognitive behavioral therapy during the short stay at our hospital, but would recommend CBT, when indicated. I found quite a lots of interventions on Saraf Hewlett's list that we use successfully in treatment of fibromyalgia patients.

I'm a bit surprised, because it's more than I had expecetd before. R. Geenen presented a chart, but I think we have to make adjustments, because we already have more information. Have a look at my chart.

To fight fatigue in rheumatoid arthritis we have to reduce inflammation and may do so with DMARDs, biologics, corticosteroids (influence on pain, morning stiffness). We can influence stuctural and functional brain changes by early and consequent therapy ("hit hard and early"), which reduce pain, morning stiffness, and stress. With graded exercise we influence the level of fitness and obesity. Reducing corticosteroids as early as possible reduces obesity. Lifestyle changes should also reduce obesity. Sleep hygine, lifestyle changes, pain controll restore sleep.

To sum it up: Fatigue needs more attention by the scientific part of rheumatology. Fatigue is complex and challenging, but it's worth the time to work on the different factors to reduce the burden of fatigue on on rheumatoid arthritis patients.

1 comment:

  1. I take issue with the studies that concentrate on this statement that you mention by R. Geenen from Utrecht University in the Netherlands “Fatigue is much more strongly correlated with cognitive variables, such as helplessness and catastrophizing thoughts, and behavioral variables, such as pacing of activities, physical fitness, and patterns of sleep and awakening”.

    After you read enough studies like that, and there are many, you get the feeling, as a patient, that fatigue is being dismissed as a somatic problem. It is often not treated by anything but sleeping pills and exercise and weight loss advice.

    I was happy to see that that you are more balanced and lay things out very clearly in your chart where you say that fatigue is in fact a real problem which may have a scientific component.