Comorbidities and complications of RA

A medical condition is referred to as comorbid when it occurs simultaneously with another condition considered to be the primary illness. So, diseases that tend to occur along with RA are said to be comorbid conditions.

There are a number of comorbid conditions that tend to appear with RA. Sometimes these conditions may also be called extra-articular (this means they appear outside of the joint) complications or manifestations of RA, when they occur as a result of the disease process involved in RA.

Comorbidities and complications of rheumatoid arthritis

RA is associated with numerous comorbidities and complications, affecting a wide range of organs and organ systems, including blood vessels, bones, the brain and nerves, the cardiovascular system, kidney, liver, eyes, and lungs.1-4

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Some of the main comorbidities associated with RA include cardiovascular disease, osteoporosis and bone loss, and infections.


Comorbidities and extra-articular manifestations of RA

Organ or Organ System
Blood vessels
  • Major cutaneous vasculitis, atherogenesis, vasculitis, Raynaud’s syndrome
  • Osteoporosis, low bone mineral density, fractures, osteomyelitis
Brain and nerves
  • Reduced cognitive function, depression, neuropathy, myelopathy, low stress tolerance
Cardiovascular system
  • Pericarditis, myocardial infarction, ischemic heart disease, congestive heart failure, stroke
  • Acute phase response, iron redistribution, altered lipid metabolism
  • Secondary Sjögren’s syndrome, periodontitis
  • Glomerulonephritis
  • Insulin resistance, sarcopenia
  • Septic arthritis
  • Scleritis, retinal vasculitis, secondary Sjögren’s syndrome, kerato-conjunctivitis sicca
  • Pleuritis, pulmonary fibrosis, bronchiolitis, pneumonia
  • Felty’s syndrome


Cardiovascular disease is a common comorbidity

Cardiovascular disease is one of the more common comorbidities associated with RA. The prevalence of a range of cardiovascular conditions is increased in patients with RA, including myocardial infarction (MI or heart attack), stroke, congestive heart failure, ischemic heart disease, and vascular disease.3

For example, results from the Nurses Health Study, a study that included over 100,000 participants, showed that women who had had RA for 10 years had 3 times the risk for MI compared with women without RA.5

Increased risk of osteoporosis and fracture

Osteoporosis, with increased risk of fracture, commonly affects women with RA. This is especially true as women reach menopause and during the post-menopausal years. In the general population, the period shortly before menopause (1.5 years before) and the period following menopause are associated with loss of bone, with bone density decreasing on average at a rate of 2.5% yearly during peri-menopause and at a slower rate (about 1%) after menopause. Among post-menopausal Caucasian women in the general population, 35% will develop osteoporosis, with increased fracture risk.6

Women with RA, who already face a risk of bone loss associated with chronic inflammation, face additional increased risk of osteoporosis from menopause. This means that they are at extremely high risk for fractures and other complications associated with continued bone loss.6

Osteoporosis and bone loss can affect women with RA well before they reach menopause. Results from a study of 394 female RA patients ranging in ages from 20 to 70 years found that bone mineral density was reduced throughout the study population and that osteoporosis occurred at double the rate for the entire group of female RA patients compared with a healthy control group of females without RA.7

Increased risk of infection

RA patients face increased risk for infections, mainly affecting joints and bones, but also affecting the skin, soft tissues, and respiratory tract. One study conducted in Rochester, Minnesota, found that RA patients faced a 10-fold increased risk for osteomyelitis (an infection of the bone or bone marrow) and a 15-fold increased risk for septic arthritis (an infection of the joint) compared with the general population. Overall, the risk for developing infections was around 50% higher in RA patients compared with the general population.8

The cause behind increased risk for infection among RA patients is unclear. There are several factors that may contribute to this increased risk, including the immune system malfunction that is part of RA, as well as use of drugs that suppress the immune system. Corticosteroids have been shown to increase risk of both mild and serious infections. Selected DMARDs with immunosuppressive potential (azathioprine, cyclosporine, cyclophosphamide, and leflunomide) have been shown to increase the risk of infection. Notably, methotrexate is not associated with increased infection risk. Newer biologic treatments are also associated with increased risk for infection.3

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Written by: Jonathan Simmons | Last reviewed: September 2013.