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Inflammation and Fatigue: What's the Link?

Carolyn Whiskin  Featured
June 11 2015 11:20 AM ET — via RheumReports RheumReports

I don't think there is a clinician who hasn't been challenged with treating fatigue in patients with chronic inflammatory disease. What is frustrating is that fatigue can persist despite achieving low disease activity. Many clinicians attended this session in the hopes of finding answers to this clinical conundrum!

This session focused on the brain and fatigue. The definition of fatigue is considered to be an overwhelming sense of tiredness, lack of energy and feeling of exhaustion that is not improved by sleep or caffeine. Between 70-80% of patients with chronic inflammatory diseases suffer from fatigue.

Over 200 scales have been developed to assess fatigue from generalized to disease-specific questionnaires. FACIT-F is one such scale. Fatigue is prevalent in many conditions including depression, cancer, chronic neurological disease (MS, Parkinson's) and autoimmune diseases.

The fatigue response in inflammatory diseases is thought to closely parallel the fatigue experienced with an active infection. During infection, there is an increase in the production of TNF, IL-1, IL-6 and HMGB1. IL-1beta crosses the blood-brain-barrier (BBB) and binds to receptors in several areas of the brain. When IL-1 is injected into the cerebral ventricles of mice, it generates a sickness/fatigue behaviour. When IL-1 blockers such as anakinra (which crosses the BBB) are used, the mice experience no fatigue.

Fatigue is a protective mechanism that allows the body to repair from insult to avoid further injury and danger. In chronic conditions of inflammation, fatigue persists. Use of anakinra in patients with auto-immune diseases has been shown to significantly reduce fatigue. There also appears to be a genetic basis to fatigue in that some genotypes increase IL-1 signalling.

Heat shock proteins are also produced in times of high inflammation and body stress. Higher fatigue levels are associated with higher levels of these proteins, which bind to specific brain neurons.

Treatment with traditional DMARDs has been shown to be of limited benefit in improving fatigue. However, all biologic treatments and the new oral small molecules, JAK inhibitors, are helpful in many patients. Aerobic exercise remains an important part of reducing fatigue but can be difficult in our population of patients. Cognitive Behavioural Therapy (CBT) has also shown benefit. 

Methotrexate-induced fatigue can contribute to the overall fatigue seen in patients with low disease activity. Strategies to reduce MTX-induced fatigue were shared during the question period, which included the use of weekly dextromethorphan in varying regimens starting the day prior to MTX administration and continuing for one day after at a dose of 30 mg b.i.d.

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About the Author

Carolyn Whiskin
Carolyn Whiskin

Carolyn Whiskin, BSc. Phm is currently the director of pharmacy programs for the Charlton Centre for Specialized Treatments in Hamilton, Ontario. She also practices pharmacy at Brant Arts Dispensary in Burlington, Ontario and is the pharmacist representative to the Ontario Rheumatology Association’s Model of Care committee.

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