Rheumatoid Arthritis (RA)

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    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.

    Rheumatoid Arthritis (RA) falls under the Pain category.

    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 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

    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.

    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.

    Examine Database: Rheumatoid Arthritis (RA)

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    Frequently asked questions

    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?

    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?

    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?

    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?

    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?

    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?

    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?

    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?

    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?

    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.

    References

    1. ^The content of this page was partially adapted from MedlinePlus of the National Library of Medicine
    2. ^National Center for Complementary and Integrative HealthRheumatoid Arthritis: In Depth
    3. ^Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto KRheumatoid arthritis.Nat Rev Dis Primers.(2018-02-08)
    4. ^Nell VP, Machold KP, Eberl G, Stamm TA, Uffmann M, Smolen JSBenefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis.Rheumatology (Oxford).(2004-Jul)
    5. ^MacGregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Aho K, Silman AJCharacterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins.Arthritis Rheum.(2000-Jan)
    6. ^Ngo ST, Steyn FJ, McCombe PAGender differences in autoimmune disease.Front Neuroendocrinol.(2014-Aug)
    7. ^Sharma A, Pandey BD, Gupta R, Chaturvedi ARheumatoid arthritis with necrotic lung nodules.J R Coll Physicians Edinb.(2020-Sep)

    Examine Database References

    1. Joint Pain (General) - 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. Joint Pain (General) - 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)
    4. 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)
    5. 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)
    6. TNF-Alpha - 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. C-Reactive Protein (CRP) - 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)
    8. 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)
    9. 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)
    10. C-Reactive Protein (CRP) - 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)
    11. C-Reactive Protein (CRP) - Chandran B, Goel AA randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritisPhytother Res.(2012 Nov)
    12. 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)
    13. C-Reactive Protein (CRP) - Pattrick M, Heptinstall S, Doherty MFeverfew in rheumatoid arthritis: a double blind, placebo controlled studyAnn Rheum Dis.(1989 Jul)
    14. 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)
    15. C-Reactive Protein (CRP) - Deutsch LEvaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptomsJ Am Coll Nutr.(2007 Feb)
    16. C-Reactive Protein (CRP) - 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)
    17. 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)
    18. Rheumatoid Arthritis Symptoms - 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)
    19. 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..()
    20. 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)
    21. 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)
    22. Rheumatoid Arthritis Symptoms - Allen M, Oberle K, Grace M, Russell AElk velvet antler in rheumatoid arthritis: phase II trialBiol Res Nurs.(2002 Jan)
    23. 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)
    24. 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)
    25. Rheumatoid Arthritis Symptoms - Gheita TA, Kenawy SAEffectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled studyPhytother Res.(2012 Aug)
    26. 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)
    27. 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)
    28. 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)
    29. Fasting 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)