Rheumatoid arthritis (RA) is an autoimmune disease in which the body’s immune system attacks its own tissue. Symptoms include pain, swelling, and stiffness of the joints. When untreated, joint damage and deformities can eventually lead to difficulty moving the hands, wrists, knees, and/or hips. RA is considered a systemic disease because it can also involve more than just joints—potentially damaging skin, blood vessels, lungs, eyes, and/or the heart.
Rheumatoid arthritis is caused by inflammation and immune-mediated damage to the body’s tissue. These effects are produced by immune cells that mistakenly attack joints, and sometimes other organs of the body as well. Several underlying risk factors increase a person’s predisposition to RA, including having other immune diseases, a family history of RA, smoking, obesity, and stress.
RA is considered an autoimmune disease. It is characterized by inflammation and tissue damage that is caused by the body’s own immune system working against itself. Excess immune cells and immune proteins chronically flood the joints and other tissue, attacking these structures as they would combat an infectious organism. There isn’t a clear trigger for the immune system overactivity.
There is a hereditary component to RA, and you may be more prone to developing the disorder if you have a family history of RA or other autoimmune conditions. Certain inherited abnormalities in the genes that direct the immune system have been identified in association with RA. And genetic changes tend to be more commonly identified among people who develop RA at a young age.
RA diagnosis relies on a combination of symptoms, clinical exam, and diagnostic tests. The physical exam shows joint tenderness and swelling. Joint inflammation and degeneration may be seen on imaging tests. Inflammatory markers, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), may be elevated in the blood. The 2010 RA Classification Criteria, a point-based system, may be used to aid in the diagnosis of RA.
Both conditions involve joint pain, and degeneration. Osteoarthritis is caused by wear and tear, and RA by immune system dysfunction. Osteoarthritis affects injured or overused joints and doesn’t involve other organs. RA affects multiple joints, and is a result of systemic disease. Prescription disease-modifying agents are a cornerstone of RA treatment, and exercise is central to osteoarthritis treatment. They don’t cause each other, but osteoarthritis and RA can coexist.
You may have joint stiffness, swelling, and tenderness with RA. The symptoms tend to be more noticeable in the morning, especially early in the disease course. And you can also have fatigue and fever. Because the early symptoms can be somewhat vague, RA can seem similar to other conditions like lupus and Lyme disease. Late signs include severe pain, joint deformity, and limited mobility.
Anti-cyclic citrullinated peptide (anti-CCP) is an antibody associated with RA. It can be measured with a blood test. Normally, anti-CCP should be less than 20 units per milliliter (u/mL), although different test kits or labs may have their own normal standards. It is elevated in approximately 60 to 70% of people who have RA, even at early stages of the disease. This antibody is not associated with other conditions, and it’s not clear what triggers its production in the body.
An autoimmune disease is a condition in which the body’s immune system attacks its own healthy tissue, resulting in harmful effects, such as pain, tissue breakdown, and sometimes permanent damage. Rheumatoid arthritis is a systemic autoimmune disease in which the joints are preferentially attacked. Most autoimmune diseases are chronic, and each disease generally targets one or a few select tissue types.
Inflammation, the body’s normal healing response to an injury or infection, should subside after an infection resolves or after healing takes place. Chronic inflammation occurs when immune cells and proteins are persistently elevated, and it can affect the whole body or may target a specific location (or locations). The effects of chronic inflammation include swelling, tissue damage, fever, and fatigue.
A C-reactive protein (CRP) blood test measures CRP, a protein that is produced by the liver and released into the blood. This protein aids the body’s immune system function, and it is released in response to inflammation.1 A normal CRP level should be lower than 10 milligrams per liter (mg/L). An elevated level is a sign of inflammation. A chronically elevated CRP level suggests chronic inflammatory disease and may point to a risk of heart disease.
Rheumatoid factor is an autoantibody. A rheumatoid factor blood test measures the amount of it in the blood, which should normally be lower than 15 IU/mL. Elevated rheumatoid factor is associated with autoimmune disease, especially RA.1 But you could have elevated levels without autoimmune disease, and you may have a normal concentration even with autoimmune disease.
The ESR is a measurement of erythrocyte (red blood cells) sedimentation (settling to the bottom). Many conditions slow down this process, raising ESR. Infections, chronic inflammation, cancer, and heart or kidney disease are among the causes of high ESR. Your ESR would be interpreted based on standards calibrated in the lab where your test is being done. A few conditions, including sickle cell anemia and polycythemia, can be associated with low ESR.
Papules are small, solid bumps on the skin. They can be red or pink. Rheumatoid papules are skin lesions that can appear with rheumatoid arthritis. They look like a patchy rash, and they can appear anywhere on the skin. Rheumatoid arthritis papules differ from rheumatoid nodules, which are large, thick, firm lumps near the joints.
Plaques are thick, scaly skin lesions. They can itch or they might not produce any discomfort. Psoriasis, an autoimmune skin disease, is characterized by plaques. Psoriatic arthritis is a type of psoriasis characterized by inflammation that affects the skin and the joints. It differs from rheumatoid arthritis in that the joint inflammation is part of the autoimmune process of psoriasis.
A synovectomy is a type of operation in which the synovium (thin, fluid-filled lining inside the joints) is surgically removed due to severe inflammation. This surgery may be done to relieve symptoms of RA or other types of joint inflammation when medication is ineffective. The inflamed synovium can be resected with a surgical blade or removed with radiation. Recovery takes three to four months, and the synovium can grow back, potentially causing symptoms again.
Mitrović J, Hrkač S, Tečer J, et al. Pathogenesis of extraarticular manifestations in rheumatoid arthritis-a comprehensive review. Biomedicines. 2023;11(5). doi:10.3390/biomedicines11051262
American College of Rheumatology. Rheumatoid arthritis. Updated March 2019.
Fatima Rizvi ST, Arif A, Azhar A. TNF gene promoter region polymorphisms and association with young-onset rheumatoid arthritis. Pak J Pharm Sci. 2019 Sep;32(5(Supplementary)):2295-2297. PMID: 31894057.
Mjaavatten MD, Bykerk VP. Early rheumatoid arthritis: the performance of the 2010 ACR/EULAR criteria for diagnosing RA. Best Pract Res Clin Rheumatol. 2013 Aug;27(4):451-66. doi: 10.1016/j.berh.2013.09.001
Cho J, Pyo JY, Fadriquela A, Uh Y, Lee JH. Comparison of the analytical and clinical performances of four anti-cyclic citrullinated peptide antibody assays for diagnosing rheumatoid arthritis. Clin Rheumatol. 2020 Sep 23. doi: 10.1007/s10067-020-05412-w
American College of Rheumatology. Rheumatoid arthritis. Updated March 2019
Jacob H, Curtis AM, Kearney CJ. Therapeutics on the clock: circadian medicine in the treatment of chronic inflammatory diseases. Biochem Pharmacol. 2020 Sep 30:114254. doi:10.1016/j.bcp.2020.114254
Nehring SM, Goyal A, Bansal P, Patel BC. C reactive protein (CRP). 2020 Jun 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–.
Alves F, Gonçalo M. Suspected inflammatory rheumatic diseases in patients presenting with skin rashes. Best Pract Res Clin Rheumatol. 2019 Aug;33(4):101440. doi:10.1016/j.berh.2019.101440
Lipina M, Makarov M, Mukhanov V, Karpashevich A, Maglevaniy S, Amirdjапоvа V, Archipov S. Arthroscopic synovectomy of the knee joint for rheumatoid arthritis. Int Orthop. 2019 Aug;43(8):1859-1863. doi:10.1007/s00264-018-4160-z
Amini A, Yahyanezhad S, Velez E, Gholamrezanezhad A, Fotoohi M, Jafari E, Assadi M. Prospective evaluation of phosphorus-32 radiation synovectomy in patients with severe and chronic rheumatoid arthritis unresponsive to conventional medical treatment. Nucl Med Commun. 2020 Jan;41(1):65-72. doi:10.1097/MNM.0000000000001116
Yan L, Liang M, Yang T, Ji J, Jose Kumar Sreena GS, Hou X, Cao M, Feng Z. The immunoregulatory role of myeloid-derived suppressor cells in the pathogenesis of rheumatoid arthritis. Front Immunol. 2020 Sep 15;11:568362. doi: 10.3389/fimmu.2020.568362