Rheumatoid Arthritis (RA)

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    Bill Willis

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    Mike Murray, Graham Walker
    Last Updated: October 13, 2024

    Rheumatoid arthritis (RA) is an autoimmune disease that is mainly known for affecting the joints, but can also affect other parts of the body. It is more common in women than men and often starts during middle age, but it can occur at any age. The cause of RA is not well understood, but it seems to involve genetic, environmental, and hormonal factors.

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    43,547 participants in 26 trials and 4 meta-analyses

    What is rheumatoid arthritis?

    Arthritis means inflammation of the joints. Unlike osteoarthritis (OA), the most common form of arthritis that is caused by general wear and tear, RA is caused by an autoimmune reaction where the immune system attacks the tissue that protects joints, leading to the characteristic pain, swelling, inflammation and eventual joint destruction. RA tends to affect the joints in a different way than OA. RA joints have a distinct, more 'squishy' type of joint swelling in contrast to the type of hard, bony enlargement of joints that is often seen in the fingers of people with OA.

    What’s the difference between osteoarthritis and rheumatoid arthritis?

    What are the main signs and symptoms of rheumatoid arthritis?

    RA symptoms often occur in the hands, wrists, knees, and feet first. Several joints can be affected at one time, and the number of joints affected may increase over time.

    RA symptoms include the following:

    • Pain and swelling in the joints — particularly the hands, feet, and knees
    • Pain and stiffness in the joints, especially after sleeping (thus worse in the mornings and improve with usage)
    • Red, puffy hands
    • Fatigue
    • Loss of appetite
    • Fever
    • Hard bumps (called rheumatoid nodules) under the skin near joints
    Are any areas of the body other than joints affected by rheumatoid arthritis?

    How is rheumatoid arthritis diagnosed?

    RA is diagnosed with a combination of medical history (having an immediate family member with RA increases risk), physical exams, X-rays, and lab tests. If RA is suspected, lab tests are performed to look for increased inflammation or signs of autoimmunity.

    Diagnostic tests for RA include the following:[1]

    • Antinuclear antibody (ANA) test
    • C-reactive protein (CRP) test
    • Cyclic citrullinated peptide (CCP) antibody test
    • Complement blood test
    • Erythrocyte sedimentation rate (ESR) test
    • Rheumatoid factor (RF) test
    • Synovial fluid analysis

    What are some of the main medical treatments for rheumatoid arthritis?

    Although there is no cure for RA, there are a number of effective treatments. RA treatments are generally designed to provide pain relief, reduce joint stiffness and inflammation, and suppress immune activity to limit further joint damage. When a diagnosis of RA is reached, treatment is started as soon as possible to limit disease activity and prevent joint damage from getting worse.

    Treatments such as NSAIDS and steroids target inflammation, which can limit joint damage and are often used in combination with treatments designed to suppress the immune system.

    What is the outlook for a patient with rheumatoid arthritis?

    Have any supplements been studied for rheumatoid arthritis?

    The following supplements have shown some promise for the relief of RA symptoms:

    How could diet affect rheumatoid arthritis?

    Although there is a clear relationship between diet and the immune system, the relationship between nutritional status and autoimmunity is not well understood. The effect of particular diets (e.g., the Mediterranean diet, vegetarian, elimination diets) on RA symptoms and pathology is currently unclear, but it's an active area of research. Therefore, people with RA should consult closely with their physician or rheumatologist before starting a special diet.[2]

    Are there any other treatments for rheumatoid arthritis?

    The following treatments have been studied for the relief of RA symptoms:[2]

    What causes rheumatoid arthritis?

    As with other autoimmune diseases, RA is caused by the immune system inappropriately targeting ‘self’ tissues or proteins. The mechanism by which this occurs is an active area of research but is not well understood. In the case of RA, the immune system targets the synovial lining of joints, causing inflammation and progressive damage to the joint and eventual loss of joint function. Both genetics and environmental factors are known to play a role in the disease, but the specific mechanisms driving the autoimmunity are not clear.

    What are the risk factors for developing rheumatoid arthritis?What does 60% “heritability” mean?Why is rheumatoid arthritis more prevalent in women compared to men?

    Examine Database: Rheumatoid Arthritis (RA)

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    Frequently asked questions

    What is rheumatoid arthritis?

    Rheumatoid arthritis (RA) is an autoimmune condition that causes inflammation of the joints when the immune system attacks protective tissue, which leads to pain, swelling, and potential joint destruction. Unlike osteoarthritis, RA results in a distinct type of "squishy" joint swelling rather than the hard, bony enlargements that are typical of osteoarthritis.

    Arthritis means inflammation of the joints. Unlike osteoarthritis (OA), the most common form of arthritis that is caused by general wear and tear, RA is caused by an autoimmune reaction where the immune system attacks the tissue that protects joints, leading to the characteristic pain, swelling, inflammation and eventual joint destruction. RA tends to affect the joints in a different way than OA. RA joints have a distinct, more 'squishy' type of joint swelling in contrast to the type of hard, bony enlargement of joints that is often seen in the fingers of people with OA.

    What’s the difference between osteoarthritis and rheumatoid arthritis?
    Quick answer:

    Osteoarthritis is caused by the progressive loss of cartilage, which leads to joint inflammation due to factors like overuse and age, whereas rheumatoid arthritis is an autoimmune disease that specifically targets and degrades joint tissue.

    Osteoarthritis is caused by a progressive loss of cartilage that leads to joint inflammation via bone-on-bone rubbing, overuse, age, and trauma, whereas rheumatoid arthritis is an autoimmune inflammatory disease that targets and degrades joint tissue.

    What are the main signs and symptoms of rheumatoid arthritis?

    Rheumatoid arthritis primarily causes pain and swelling in the joints, particularly in the hands, feet, and knees, and often worsens in the mornings and improves with movement. Additional symptoms may include red puffy hands, fatigue, loss of appetite, fever, and the presence of rheumatoid nodules under the skin.

    RA symptoms often occur in the hands, wrists, knees, and feet first. Several joints can be affected at one time, and the number of joints affected may increase over time.

    RA symptoms include the following:

    • Pain and swelling in the joints — particularly the hands, feet, and knees
    • Pain and stiffness in the joints, especially after sleeping (thus worse in the mornings and improve with usage)
    • Red, puffy hands
    • Fatigue
    • Loss of appetite
    • Fever
    • Hard bumps (called rheumatoid nodules) under the skin near joints
    Are any areas of the body other than joints affected by rheumatoid arthritis?
    Quick answer:

    Rheumatoid arthritis can affect areas beyond the joints, including the eyes, lungs, heart, and other organs. It may also lead to the formation of rheumatoid nodules, vasculitis, and an increased risk of cardiovascular and lung disorders.

    Although RA is associated with joint disorders, the disease can also affect other parts of the body. The eyes, lungs, and heart, as well as other organs can be affected. Lumps of inflamed tissue called rheumatoid nodules often form under the skin near affected joints, but they can also occur in other areas of the body, such as the lungs.[7] Additionally, RA can cause vasculitis (i.e., inflammation of the blood vessels) and patients have been reported to develop fibromyalgia. Cardiovascular disease and lung disorders are also more common with RA.

    How is rheumatoid arthritis diagnosed?

    Rheumatoid arthritis is diagnosed through a combination of medical history, physical exams, X-rays, and lab tests that assess inflammation and autoimmunity. Key diagnostic tests include the ANA test, CRP test, CCP antibody test, complement blood test, ESR test, RF test, and synovial fluid analysis.

    RA is diagnosed with a combination of medical history (having an immediate family member with RA increases risk), physical exams, X-rays, and lab tests. If RA is suspected, lab tests are performed to look for increased inflammation or signs of autoimmunity.

    Diagnostic tests for RA include the following:[1]

    • Antinuclear antibody (ANA) test
    • C-reactive protein (CRP) test
    • Cyclic citrullinated peptide (CCP) antibody test
    • Complement blood test
    • Erythrocyte sedimentation rate (ESR) test
    • Rheumatoid factor (RF) test
    • Synovial fluid analysis
    What are some of the main medical treatments for rheumatoid arthritis?

    Rheumatoid arthritis has no cure, but effective treatments aim to relieve pain, reduce inflammation, and suppress immune activity to prevent further joint damage. Common treatments include nonsteroidal anti-inflammatory drugs and steroids, which are often used alongside immune-suppressing therapies and are initiated promptly after diagnosis to limit disease progression.

    Although there is no cure for RA, there are a number of effective treatments. RA treatments are generally designed to provide pain relief, reduce joint stiffness and inflammation, and suppress immune activity to limit further joint damage. When a diagnosis of RA is reached, treatment is started as soon as possible to limit disease activity and prevent joint damage from getting worse.

    Treatments such as NSAIDS and steroids target inflammation, which can limit joint damage and are often used in combination with treatments designed to suppress the immune system.

    What is the outlook for a patient with rheumatoid arthritis?
    Quick answer:

    The outlook for people with rheumatoid arthritis has significantly improved due to better understanding and more effective treatments, which allows many to achieve remission. Early diagnosis and treatment are crucial for managing the disease and controlling its progression.

    According to a review paper published in 2018, the outlook for patients with RA has reached a point that nobody would have even dreamed of 20 years ago. Although RA can progress to be an incredibly disabling disease, an increased understanding of the disease biology and more effective treatments have turned it into a very manageable disease, with many patients reaching a state of remission.[3] With that said, it is important for people with RA to see a physician and begin treatment as soon as possible because early diagnosis and treatment are key to controlling disease progression.[4]

    Have any supplements been studied for rheumatoid arthritis?

    Several supplements have shown promise for relieving rheumatoid arthritis symptoms, including omega-3 fatty acids, gamma-linolenic acid (GLA), thunder god vine, and probiotics.

    The following supplements have shown some promise for the relief of RA symptoms:

    How could diet affect rheumatoid arthritis?

    The relationship between diet and rheumatoid arthritis (RA) is not well understood, although there is a connection between diet and the immune system. People with RA should consult their physician before starting any special diet because the effects of specific diets on RA symptoms are still a topic of ongoing research.

    Although there is a clear relationship between diet and the immune system, the relationship between nutritional status and autoimmunity is not well understood. The effect of particular diets (e.g., the Mediterranean diet, vegetarian, elimination diets) on RA symptoms and pathology is currently unclear, but it's an active area of research. Therefore, people with RA should consult closely with their physician or rheumatologist before starting a special diet.[2]

    Are there any other treatments for rheumatoid arthritis?

    Various treatments have been studied for relieving rheumatoid arthritis symptoms, including acupuncture, massage, mindfulness meditation, tai chi, yoga, Ayurvedic medicine, and balneotherapy. These alternative therapies may provide additional options for managing the condition.

    The following treatments have been studied for the relief of RA symptoms:[2]

    What causes rheumatoid arthritis?

    Rheumatoid arthritis is caused by the immune system mistakenly attacking the body's own tissues, particularly the synovial lining of joints, which leads to inflammation and joint damage. Although both genetic and environmental factors contribute to the disease, the exact mechanisms behind this autoimmune response remain unclear.

    As with other autoimmune diseases, RA is caused by the immune system inappropriately targeting ‘self’ tissues or proteins. The mechanism by which this occurs is an active area of research but is not well understood. In the case of RA, the immune system targets the synovial lining of joints, causing inflammation and progressive damage to the joint and eventual loss of joint function. Both genetics and environmental factors are known to play a role in the disease, but the specific mechanisms driving the autoimmunity are not clear.

    What are the risk factors for developing rheumatoid arthritis?
    Quick answer:

    Risk factors for developing rheumatoid arthritis (RA) include female sex, genetic predisposition, and various environmental factors such as smoking, silica exposure, vitamin D deficiency, and obesity. Additionally, certain variants of the human leukocyte antigen genes are strongly associated with an increased risk of RA.

    There are a number of factors that have been associated with increased risk of developing RA, including female sex, genetics, and environmental factors. Some of the environmental risk factors include a history of smoking, exposure to silica (via dust or occupational exposure) or infectious agents, vitamin D deficiency, and obesity. There is also a significant genetic component to RA. Studies in twins have estimated that RA may have around 60% heritability.[5] Certain variants of the human leukocyte antigen (HLA) genes, which encode proteins that are important for the function of the immune system, have strong risk associations with RA.

    What does 60% “heritability” mean?
    Quick answer:

    A heritability of 60% indicates that 60% of the variation in rheumatoid arthritis within a population is due to genetic differences, rather than environmental factors. However, this figure does not imply that any individual with RA has 60% of their condition caused by genetics because heritability is a population-level measure, not an individual one.

    Technically speaking, heritability estimates the amount of phenotypic variation (i.e., the variation in a certain trait, such as having RA) that is caused by variation in genes in a given population. An easier way to understand the concept is to consider the extremes. A heritability of 100% would indicate that RA (or the trait in question) could be 100% attributed to genetics and 0% to environmental factors. In contrast, a heritability of 0% would indicate that genetics were not involved whatsoever in developing the disease. It is important to note that “60% heritability” does not mean that, in any individual with RA, 60% of the cause can be chalked up to genetics. (Heritability is defined only at the population level, not at the individual level.) It also does not mean that 60% of individuals with RA have RA because of their genetic makeup.

    Why is rheumatoid arthritis more prevalent in women compared to men?
    Quick answer:

    Women are 2 to 3 times more likely to develop rheumatoid arthritis (RA) than men, which may be partially attributed to the effects of higher estrogen levels on the immune system. However, the precise role of hormones in RA development remains unclear.

    Women are 2–3 times more likely to develop RA than men.[6] The increased incidence of RA (and autoimmune disease in general) in women can be partially explained by the effects of higher estrogen levels on the immune system, but the exact role of hormones in the development of RA is not well understood.

    Examine Database References

    1. Pain - Katja A Schönenberger, Anne-Catherine Schüpfer, Viktoria L Gloy, Paul Hasler, Zeno Stanga, Nina Kaegi-Braun, Emilie ReberEffect of Anti-Inflammatory Diets on Pain in Rheumatoid Arthritis: A Systematic Review and Meta-AnalysisNutrients.(2021 Nov 24)
    2. Interleukin 6 - Hulander, E; et al.A randomized controlled cross-over trial investigating the acute inflammatory and metabolic response after meals based on red meat, fatty fish, or soy protein: the postprandial inflammation in rheumatoid arthritis (PIRA) trialEur J Nutr.(2024-06-27)
    3. Pain - Amalraj A, Varma K, Jacob J, Divya C, Kunnumakkara AB, Stohs SJ, Gopi SA Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group StudyJ Med Food.(2017 Oct)
    4. Pain - Chandran B, Goel AA randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritisPhytother Res.(2012 Nov)
    5. Pain - Kirkeskov B, Christensen R, Bügel S, Bliddal H, Danneskiold-Samsøe B, Christensen LP, Andersen JRThe effects of rose hip (Rosa canina) on plasma antioxidative activity and C-reactive protein in patients with rheumatoid arthritis and normal controls: a prospective cohort studyPhytomedicine.(2011 Aug 15)
    6. Pain - Willich SN, Rossnagel K, Roll S, Wagner A, Mune O, Erlendson J, Kharazmi A, Sörensen H, Winther KRose hip herbal remedy in patients with rheumatoid arthritis - a randomised controlled trialPhytomedicine.(2010 Feb)
    7. Pain - Trentham DE, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, Hafler DA, Weiner HLEffects of oral administration of type II collagen on rheumatoid arthritisScience.(1993 Sep 24)
    8. Pain - Barnett ML, Kremer JM, St Clair EW, Clegg DO, Furst D, Weisman M, Fletcher MJ, Chasan-Taber S, Finger E, Morales A, Le CH, Trentham DETreatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trialArthritis Rheum.(1998 Feb)
    9. Rheumatoid Arthritis Symptoms - M L Barnett, D Combitchi, D E TrenthamA pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritisArthritis Rheum.(1996 Apr)
    10. Pain - Gheita TA, Kenawy SAEffectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled studyPhytother Res.(2012 Aug)
    11. Pain - Brosseau L, Robinson V, Wells G, Debie R, Gam A, Harman K, Morin M, Shea B, Tugwell PLow level laser therapy (Classes I, II and III) for treating rheumatoid arthritis.Cochrane Database Syst Rev.(2005-Oct-19)
    12. TNF-Alpha - Zahra Hamidi, Naheed Aryaeian, Jamileh Abolghasemi, Fatemeh Shirani, Mahsa Hadidi, Soudabeh Fallah, Nariman MoradiThe effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trialPhytother Res.(2020 Jul)
    13. TNF-Alpha - Hussain SA, Abood SJ, Gorial FIThe adjuvant use of calcium fructoborate and borax with etanercept in patients with rheumatoid arthritis: Pilot studyJ Intercult Ethnopharmacol.(2016 Dec 8)
    14. TNF-Alpha - Koushki M, Dashatan NA, Meshkani REffect of Resveratrol Supplementation on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials.Clin Ther.(2018-Jul)
    15. C-Reactive Protein (CRP) - Armita Mahdavi Gorabi, Saeed Aslani, Danyal Imani, Bahman Razi, Thozhukat Sathyapalan, Amirhossein SahebkarEffect of resveratrol on C-reactive protein: An updated meta-analysis of randomized controlled trialsPhytother Res.(2021 Dec)
    16. C-Reactive Protein (CRP) - Kometani T, Fukuda T, Kakuma T, Kawaguchi K, Tamura W, Kumazawa Y, Nagata KEffects of alpha-glucosylhesperidin, a bioactive food material, on collagen-induced arthritis in mice and rheumatoid arthritis in humansImmunopharmacol Immunotoxicol.(2008)
    17. C-Reactive Protein (CRP) - Pattrick M, Heptinstall S, Doherty MFeverfew in rheumatoid arthritis: a double blind, placebo controlled studyAnn Rheum Dis.(1989 Jul)
    18. C-Reactive Protein (CRP) - Ann-Charlotte Elkan, Beatrice Sjöberg, Björn Kolsrud, Bo Ringertz, Ingiäld Hafström, Johan FrostegårdGluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized studyArthritis Res Ther.(2008)
    19. C-Reactive Protein (CRP) - Deutsch LEvaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptomsJ Am Coll Nutr.(2007 Feb)
    20. C-Reactive Protein (CRP) - Abdollahzad H, et alCoenzyme Q10 supplementation in patients with rheumatoid arthritis: Are there any effects on cardiovascular risk factors?Eur J Integr Med..()
    21. Oxidative Stress Biomarkers - Sekiya N, Shimada Y, Niizawa A, Kogure T, Mantani N, Sakai S, Hikiami H, Terasawa KSuppressive effects of Stephania tetrandra on the neutrophil function in patients with rheumatoid arthritisPhytother Res.(2004 Mar)
    22. Oxidative Stress Biomarkers - Tavakoli A, Akhgarjand C, Ansar H, Houjaghani H, Khormani A, Djafarian K, Rostamian A, Ranjbar M, Farsani GMThe effects of intermittent fasting on antioxidant and inflammatory markers and liver enzymes in postmenopausal, overweight and obese women with rheumatoid arthritis: a randomized controlled trial.Sci Rep.(2025 Jan 18)
    23. Rheumatoid Arthritis Symptoms - Allen M, Oberle K, Grace M, Russell A, Adewale AJA randomized clinical trial of elk velvet antler in rheumatoid arthritisBiol Res Nurs.(2008 Jan)
    24. Rheumatoid Arthritis Symptoms - Allen M, Oberle K, Grace M, Russell AElk velvet antler in rheumatoid arthritis: phase II trialBiol Res Nurs.(2002 Jan)
    25. Rheumatoid Arthritis Symptoms - Bae SC, Jung WJ, Lee EJ, Yu R, Sung MKEffects of antioxidant supplements intervention on the level of plasma inflammatory molecules and disease severity of rheumatoid arthritis patientsJ Am Coll Nutr.(2009 Feb)
    26. Rheumatoid Arthritis Symptoms - Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, Cáceres DDEfficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trialClin Rheumatol.(2009 Aug)
    27. Rheumatoid Arthritis Symptoms - Karimi E, Aryaeian N, Akhlaghi M, Abolghasemi J, Fallah S, Heydarian A, Rostami R, Bayat MH, Mahmoudi MThe effect of purslane supplementation on clinical outcomes, inflammatory and antioxidant markers in patients with rheumatoid arthritis: A parallel double-blinded randomized controlled clinical trial.Phytomedicine.(2024 Sep 11)
    28. Weight - Barbara C Olendzki, Katherine Leung, Susan Van Buskirk, George Reed, Robert B ZurierTreatment of rheumatoid arthritis with marine and botanical oils: influence on serum lipidsEvid Based Complement Alternat Med.(2011)
    29. Rheumatoid Arthritis Risk - Karlson EW, Shadick NA, Cook NR, Buring JE, Lee IMVitamin E in the primary prevention of rheumatoid arthritis: the Women's Health StudyArthritis Rheum.(2008 Nov 15)
    30. Blood glucose - Norouzi M, Rezvankhah B, Haeri MR, Heydari H, Tafaroji J, Shafigh N, Avval JO, Dahmardeh AR, Masoumzadeh N, Gharehbeglou MMagnesium supplementation and insulin resistance in patients with rheumatoid arthritis.Eur J Transl Myol.(2022-Jul-05)