How Rheumatoid Arthritis (RA) Causes Fatigue

The root cause of fatigue in people with rheumatoid arthritis is difficult to pinpoint. It is likely that there is no single cause, but rather many factors acting independently or in concert that contribute to fatigue.

See Rheumatoid Arthritis and Fatigue

For example, in one research article experts theorize that there is a reinforcing cycle that leads to chronic fatigue:

Disease activity leads to—
Mood disturbances, such as depression and anxiety, which lead to—
Poor sleep quality, which leads to—

See Getting the Sleep You Need With Fibromyalgia

Additional clinical research supports the notion that fatigue is only indirectly related to disease activity,2,3 but more research is needed before experts can draw a decisive conclusion.

See Identifying Underlying Medical Issues That Cause RA Fatigue

Possible Factors Involved in Fatigue

The factors below are associated with RA fatigue, meaning each factor may cause fatigue—directly or indirectly—or is simply correlated with it.

Disease activity
Rheumatoid arthritis is an autoimmune disease that causes inflammation in the joints. The immune system cells can release substances called cytokines, proteins that act as messengers throughout the body. Rheumatoid arthritis disease activity can spur a release of cytokines that lead to inflammation that leads to joint pain and possibly fatigue.

See Rheumatoid Arthritis (RA) Symptoms


Between 20% and 60% of people with rheumatoid arthritis have abnormally low levels of red blood cells, a condition called anemia. People with anemia may experience fatigue along with other symptoms, including but not limited to pale skin, dizziness, or irregular heartbeat.

Some people with RA experience anemia as a result of chronic inflammation. Others may experience iron deficiency anemia because of chronic use of NSAID medications for treatment of arthritis pain.4

Not everyone agrees with the idea that anemia is the cause of RA chronic fatigue. At least one study found that patients’ fatigue correlated with RA disease activity (e.g. tender joints) rather than anemia.5


Drug-related side effects
Many drugs can induce fatigue or related symptoms:

  • Methotrexate (Rheumatrex, Trexall, Otrexup) is an oral medication used to treat rheumatoid arthritis that causes a deficiency in the nutrient folate, which in turn can cause fatigue. People who take methotrexate typically take folate supplements.
  • Hydroxychloroquine (Plaquenil) is an oral medication used to treat rheumatoid arthritis in patients who do not respond well to methotrexate. Possible side effects of hydroxychloroquine include weakness and dizziness and, rarely, anemia.
  • Oral NSAIDs increase the risk of anemia, which can cause drowsiness. In addition, certain NSAIDs can cause sleepiness or dizziness.6,7
  • Many medications used to treat conditions such as high cholesterol, high blood pressure, and diabetes can also cause fatigue. People concerned with chronic fatigue should ask their doctors to review their complete lists of medications and supplements to consider potential side effects. Moreover, information should be shared with other members of the health care team, such as nurse practitioners and physician assistants.

In addition to the above disease-related issues that can contribute to chronic fatigue, there are a number of lifestyle and other factors that play a role.


  • 1.Nicassio PM, Ormseth SR, Custodio MK, Irwin MR, Olmstead R, Weisman MH. A multidimensional model of fatigue in patients with rheumatoid arthritis. J Rheumotol. Sep 20012; 39(9):1807-1813.
  • 2.Minnock P, McKee G, Bresnihan B, FitzGerald O, Veale D. How much is fatigue explained by standard clinical characteristics of disease activity in patients with inflammatory arthritis: a longitudinal study. Arthritis Care Res (Hoboken). 2014 Jun 25. doi: 10.1002/acr.22387. [Epub ahead of print] PubMed PMID: 24966144.
  • 3.Bergman MJ, Shahouri SS, Shaver TS, et al. Is fatigue an inflammatory variable in rheumatoid arthritis (RA)? Analyses of fatigue in RA, osteoarthritis, and fibromyalgia. J Rheumatol 2009; 36:2788-2794.
  • 4.Klippel JH et al, eds. Primer on Rheumatic Diseases, 13th edition. (pg 118) Springer. 2008.
  • 5.Singh H, Arya S, Talapatra P, Lather K, Mathur R, Singhania A, Chaudhary V. Assessment of fatigue in rheumatoid arthritis (by functional assessment of chronic illness therapy-fatigue score) and its relation to disease activity and anemia. J Clin Rheumatol. 2014 Mar; 20(2):87-90. doi: 10.1097/RHU.0000000000000073. PubMed PMID: 24561411.
  • 6.United Kingdom National Health Service. Non-steriodal anti-inflammatory drugs (NSAIDS) – side effects. NHS Choices: Your health, your choices Last reviewed April 6, 2014. Accessed December 1, 2014.
  • 7.National Institutes of Health. Naproxen. MedlinePlus. Last Revised July 14, 2013. Accessed December 1, 2014.