Understanding Rheumatoid Arthritis: Risk - Signs - Symptoms
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 8/16/2018
Rheumatoid arthritis (RA) affects an estimated 1.3 million adults in the United States.1 The condition can have a profound effect on many aspects of daily life, and is often poorly understood by those who do not have direct experience it. The good news is that important advances have been made in the management of RA: use of more effective drugs earlier in the course of RA reduces symptoms and joint damage, and allows some patients to achieve a remission (little or no active disease).2
The course of RA over a lifetime varies across individuals and is also influenced by treatment. Some people may experience a single episode that resolves within a few months or years, others may experience fluctuating symptoms (periods of few symptoms followed by periods of worse symptoms, or “flares”), and still others may have symptoms that get progressively worse.
Although there is no cure for RA, early detection and effective treatment can substantially reduce pain and disability for many individuals.
Risk Factors for Developing Rheumatoid Arthritis
It is important to understand that the cause, of Rheumatoid Arthritis is unknown.
Many cases are believed to result from an interaction between genetic factors and environmental exposures. There is however some evidence on which individuals are more likely to develop RA and modifiable risk factors that can clearly make RA worse.
Age and Gender: The incidence of RA is typically two to three times higher in women than men and the initial onset of RA, in both women and men, is highest among those in their sixties.
Genetics: There is longstanding evidence that specific HLA class II genotypes are associated with increased risk of developing RA.
Modifiable Risk Factors: Several modifiable risk factors have been studied and include the following:
- Smoking: Smoking is the strongest and most consistent modifiable risk factor for RA. A history of smoking is associated with a modest to moderate (1.3 to 2.4 times) increased risk of RA onset and the relationship between smoking and RA is strongest among people who are ACPA-positive (anti-citrullinated protein/peptide antibodies) which is a biomarker of auto-immune activity.
- Reproductive and Breastfeeding History: Hormones related to reproduction are potential risk factors for RA.
- Oral Contraceptives (OC): Although early studies found that women who had taken OCs had a modest to moderate decrease in risk of RA the most recent studies have not. This may be because the estrogen concentration of currently available OCs is significantly lower than for the pills studied in the 1960s.
- Hormone Replacement therapy (HRT): There is mixed evidence of an association between HRT and RA onset.
- Live Birth History: Most studies have found that women who have never had a live birth have a slight to moderately increased risk of RA.
- Breastfeeding: Almost all recent population based studies have found that RA is less common among women who breastfeed.
- Menstrual History: At least two studies have observed that women with irregular menses or a truncated menstrual history (e.g., early menopause) have an increased risk of RA. Because women with polycystic ovarian syndrome (PCOS) have an increased risk of RA, the association with an irregular menstrual history may result from PCOS.
Symptoms & Signs of Rheumatoid Arthritis
The symptoms of RA are familiar to many: the condition causes pain, swelling, and stiffness of joints. The joints of the wrist and hand are often involved, but RA can affect other joints as well. Joint stiffness tends to be worse in the morning or after a long rest.
To understand how RA affects joints, it first helps to understand some of the components of a healthy joint. A joint refers to a place in the body where two or more bones meet. The ends of the bones are covered in cartilage, which absorbs shock and allows the joint to work more smoothly. Surrounding the joint is a protective capsule that is lined with tissue called synovium. The synovium produces fluid that nourishes and lubricates the joint.1
In RA, the synovium becomes inflamed. The inflammation causes the joint pain and swelling, and can also damage bone and cartilage in the joint. This damage to bone and cartilage is thought to begin early in the course of the disease, highlighting the important of early diagnosis and treatment. Surrounding muscles, ligaments, and tendons can also be affected.
Symptoms related to inflammation
- Prolonged morning stiffness of the spine lasting hours
- Spine stiffness associated with sitting for variable lengths of time
- Back pain improvement with exercise
- Eye inflammation – iritis
- Radiating leg pain – pseudosciatica
Other Effects of RA
Rheumatoid arthritis can affect the entire body, particularly if the RA becomes severe.2 In addition to joint problems, people with RA may notice occasional fevers, fatigue, and a sense of being generally unwell. RA can lead to anemia (low red blood cell count) and, less commonly, to problems with the blood vessels, lungs, heart, and other organs.
General Symptoms of RA
- Disordered sleep
- Mild weight loss
RA is an autoimmune disease. An autoimmune disease occurs when the immune system—which normally protects the body from infection—turns against some of the body’s own tissues. Other examples of autoimmune diseases are Type I diabetes, lupus, Sjogren syndrome, Grave’s Disease, and multiple sclerosis.
In the case of RA, the immune system attacks the synovium and causes inflammation. It’s unclear what starts this process, but some combination of genetic and environmental factors is likely to play a role. Factors that increase the likelihood of RA include being female, smoking, and having a family history of rheumatoid arthritis.3,4
Although family history may contribute to RA, it does not entirely explain an individual’s risk. Many people with a family history of RA will never develop the condition themselves. Similarly, RA may develop in someone with no family history of the condition.
RA is not contagious (people cannot “catch” RA from someone else).
What are rheumatoid nodules?
Rheumatoid nodules are firm lumps located just under the skin. The nodules most commonly grow close to the affected joints and can be as small as a pea and as large as a chestnut. The nodules can be firmly connected to tendons or fascia under the skin or quite moveable. Rheumatoid nodules are also often found at pressure points, including the hands, fingers, knuckles, or elbows; however, they may appear almost anywhere, including the lungs, heart, other internal organs, and even on the vocal cords, causing hoarseness.
Nodules can be asymptomatic or quite painful, but they are typically not problematic unless they interfere with daily activities by putting pressure on nerves or by limiting joint movement. Rheumatoid nodules in areas such as the heart and lungs may affect organ function.
What are the causes of rheumatoid nodules?
Rheumatoid nodules usually occur in patients with more severe disease. Nearly all patients with nodules will test positive for rheumatoid factor, and studies have suggested that when RA is linked with a positive rheumatoid factor test, it may indicate more aggressive disease. Other risk factors that may lead to the development of rheumatoid nodules include cigarette smoking and the use of Methotrexate, a drug commonly used to treat RA.
1 National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Disease. Handout on Health: Rheumatoid Arthritis.
2 Young A, Koduri G. Extra-articular manifestations and complications of rheumatoid arthritis. Best Practice & Research Clinical Rheumatology. 2007;21:907-27.
4 Hemminki K, Li X, Sundquist J, Sundquist K. Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions. Arthritis & Rheumatism. 2009;60:661-668.
- Brooks PM. The burden of musculoskeletal disease–a global perspective. Clin Rheumatol.2006;25(6):778-781. PubMed PMID: 1660982.
- Silman AJ, Hochberg MC. Epidemiology of the rheumatic diseases. 2nd edition: Oxford University Press; 2001.
- Graudal NA, Jurik AG, de Carvalho A, Graudal HK. Radiographic progression in rheumatoid arthritis: a long-term prospective study of 109 patients. Arthritis Rheum. 1998;41(8):1470-1480. PubMed PMID: 9704647.
- Masi AT, Maldonado-Cocco JA, Kaplan SB, Feigenbaum SL, Chandler RW. Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome. Semin Arthritis Rheum.1976;4(4):299-326. PubMed PMID: 1273600.
- Crowson CS, Matteson EL, Myasoedova E, et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis Rheum. 2011;63(3):633-639. doi: 10.1002/art.30155. PubMed PMID: 21360492; PubMed Central PMCID: PMC3078757.