Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.
- Signs and symptoms
- Heart and blood vessels
- Blood tests
- Classification Criteria
- Differential diagnoses
- Monitoring progression
- Disease modifying agents
- Anti inflammatory agents
- Alternative medicine
- Dietary supplements
- Prognostic factors
While the cause of rheumatoid arthritis is not clear, it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves the body's immune system attacking the joints. This results in inflammation and thickening of the joint capsule. It also affects the underlying bone and cartilage. The diagnosis is made mostly on the basis of a person's signs and symptoms. X-rays and laboratory testing may support a diagnosis or exclude other diseases with similar symptoms. Other diseases that may present similarly include systemic lupus erythematosus, psoriatic arthritis, and fibromyalgia among others.
The goal of treatment is to reduce pain, decrease inflammation, and improve a person's overall functioning. This may be helped by balancing rest and exercise, the use of splints and braces, or the use of assistive devices. Pain medications, steroids, and NSAIDs are frequently used to help with symptoms. A group of medications called disease-modifying antirheumatic drugs (DMARDs), such as hydroxychloroquine and methotrexate, may be used to try to slow the progression of disease. Biological DMARDs may be used when disease does not respond to other treatments. However, they may have a greater rate of adverse effects. Surgery to repair, replace, or fuse joints may help in certain situations. Most alternative medicine treatments are not supported by evidence.
RA affects between 0.5 and 1% of adults in the developed world with between 5 and 50 per 100,000 people newly developing the condition each year. Onset is most frequent during middle age and women are affected 2.5 times as frequently as men. In 2013, it resulted in 38,000 deaths up from 28,000 deaths in 1990. The first recognized description of RA was made in 1800 by Dr. Augustin Jacob Landré-Beauvais (1772–1840) of Paris. The term rheumatoid arthritis is based on the Greek for watery and inflamed joints.
Signs and symptoms
RA primarily affects joints, but it also affects other organs in more than 15–25% of individuals.
Arthritis of joints involves inflammation of the synovial membrane. Joints become swollen, tender and warm, and stiffness limits their movement. With time, multiple joints are affected (polyarthritis). Most commonly involved are the small joints of the hands, feet and cervical spine, but larger joints like the shoulder and knee can also be involved. Synovitis can lead to tethering of tissue with loss of movement and erosion of the joint surface causing deformity and loss of function.
RA typically manifests with signs of inflammation, with the affected joints being swollen, warm, painful and stiff, particularly early in the morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the disease and typically lasts for more than an hour. Gentle movements may relieve symptoms in early stages of the disease. These signs help distinguish rheumatoid from non-inflammatory problems of the joints, such as osteoarthritis. In arthritis of non-inflammatory causes, signs of inflammation and early morning stiffness are less prominent with stiffness typically less than one hour, and movements induce pain caused by mechanical arthritis. The pain associated with RA is induced at the site of inflammation and classified as nociceptive as opposed to neuropathic. The joints are often affected in a fairly symmetrical fashion, although this is not specific, and the initial presentation may be asymmetrical.
As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity. The fingers may suffer from almost any deformity depending on which joints are most involved. Specific deformities, which also occur in osteoarthritis, include ulnar deviation, boutonniere deformity (also "buttonhole deformity", flexion of proximal interphalangeal joint and extension of distal interphalangeal joint), swan neck deformity (hyperextension at proximal interphalangeal joint and flexion at distal interphalangeal joint) and "Z-thumb." "Z-thumb" or "Z-deformity" consists of hyperextension of the interphalangeal joint, fixed flexion and subluxation of the metacarpophalangeal joint and gives a "Z" appearance to the thumb. The hammer toe deformity may be seen. In the worst case, joints are known as arthritis mutilans due to the mutilating nature of the deformities.
The rheumatoid nodule, which is sometimes in the skin, is the most common non joint feature. They occur in 30% of people who have RA. It is a type of inflammatory reaction known to pathologists as a "necrotizing granuloma". The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both. The nodule has a central area of fibrinoid necrosis that may be fissured and which corresponds to the fibrin-rich necrotic material found in and around an affected synovial space. Surrounding the necrosis is a layer of palisading macrophages and fibroblasts, corresponding to the intimal layer in synovium and a cuff of connective tissue containing clusters of lymphocytes and plasma cells, corresponding to the subintimal zone in synovitis. The typical rheumatoid nodule may be a few millimetres to a few centimetres in diameter and is usually found over bony prominences, such as the elbow, the heel, the knuckles, or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF (rheumatoid factor) titer, ACPA, and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on the body..
Several forms of vasculitis occur in RA, but are mostly seen with long-standing and untreated disease. The most common presentation is due to involvement of small- and medium-sized vessels. Rheumatoid vasculitis can thus commonly present with skin ulceration and vasculitic nerve infarction known as mononeuritis multiplex.
Other, rather rare, skin associated symptoms include pyoderma gangrenosum, Sweet's syndrome, drug reactions, erythema nodosum, lobe panniculitis, atrophy of finger skin, palmar erythema, and skin fragility (often worsened by corticosteroid use)..
Fibrosis of the lungs is a recognized complication of rheumatoid arthritis. It is also a rare but well-recognized consequence of therapy (for example with methotrexate and leflunomide). Caplan's syndrome describes lung nodules in individuals with RA and additional exposure to coal dust. Exsudative Pleural effusions are also associated with RA.
Renal amyloidosis can occur as a consequence of untreated chronic inflammation. Treatment with penicillamine and gold salts are recognized causes of membranous nephropathy.
Heart and blood vessels
People with RA are more prone to atherosclerosis, and risk of myocardial infarction (heart attack) and stroke is markedly increased. Other possible complications that may arise include: pericarditis, endocarditis, left ventricular failure, valvulitis and fibrosis. Many people with RA do not experience the same chest pain that others feel when they have angina or myocardial infarction. To reduce cardiovascular risk, it is crucial to maintain optimal control of the inflammation caused by RA (which may be involved in causing the cardiovascular risk), and to use exercise and medications appropriately to reduce other cardiovascular risk factors such as blood lipids and blood pressure. Doctors who treat people with RA should be sensitive to cardiovascular risk when prescribing anti-inflammatory medications, and may want to consider prescribing routine use of low doses of aspirin if the gastrointestinal effects are tolerable.
RA is a chronic autoimmune disorder the causes of which are not completely understood. It is a systemic (whole body) disorder principally affecting synovial tissues. There is no evidence that physical and emotional effects or stress could be a trigger for the disease. The many negative findings suggest that either the trigger varies, or that it might, in fact, be a chance event inherent with the immune response.
Half of the risk for RA is believed to be genetic. It is strongly associated with the inherited tissue type major histocompatibility complex (MHC) antigen HLA-DRB1 (most specifically the shared epitope alleles, including *0401 and *0404, although this difference based in race and ethnicity), and the genes PTPN22 and PADI4—hence family history is an important risk factor. Inheriting the PTPN22 gene has been shown to double a person's susceptibility to RA. PADI4, the gene encoding one of the human citrullinating enzymes, has been identified as a major risk factor in people of Asian descent, but not in those of European descent. First-degree relatives prevalence rate is 2–3% and disease genetic concordance in monozygotic twins is approximately 15–20%.
Smoking may be the most significant non-genetic risk factor for RA in Caucasian populations, with RA being up to three times more common in smokers than non-smokers, particularly in men, heavy smokers, and those who are rheumatoid factor positive. Modest alcohol consumption may be protective.
Both genetic, as well as environmental factors, are implicated in the pathophysiology of the disease. Smoking is the main environmental risk to RA. 50% of the risk of having RA is attributable to genetic factors. No infectious agent has been consistently linked with RA and there is no evidence of disease clustering to indicate its infectious cause. HLA-DR4 is the major genetic factor implicated – but its relative importance varies across ethnic groups. Related allotypes of MHC Class II and the T cell-associated protein PTPN22 has also been found associated in many studies.
RA primarily starts as a state of persistent cellular activation leading to autoimmunity and immune complexes in both joints and other, organs where it manifests. The initial site of disease is the synovial membrane, where swelling and congestion leads to infiltration by immune cells. The various phases of progression of RA are:
The factors that allow an abnormal immune response, once initiated, to become permanent and chronic, are becoming more clearly understood. The genetic association with HLA-DR4, as well as the newly discovered associations with the gene PTPN22 and with two additional genes, all implicate altered thresholds in regulation of the adaptive immune response. It has also become clear from recent studies that these genetic factors may interact with the most clearly defined environmental risk factor for RA, namely cigarette smoking. Other environmental factors also appear to modulate the risk of acquiring RA, and hormonal factors in the individual may explain some features of the disease, such as the higher occurrence in women, the not-infrequent onset after childbirth, and the (slight) modulation of disease risk by hormonal medications. Exactly how altered regulatory thresholds allow the triggering of a specific autoimmune response remains uncertain. However, one possibility is that negative feedback mechanisms that normally maintain tolerance of self are overtaken by aberrant positive feedback mechanisms for certain antigens such as IgG Fc (bound by RF) and citrullinated fibrinogen (bound by ACPA) (see the entry on autoimmunity).The debate on the relative roles of immune complexes and T cell products in inflammation in RA has continued for 30 years. There is little doubt that both B and T cells are essential to the disease. However, there is good evidence for neither cell being necessary at the site of inflammation. This tends to favor immune complexes (based on antibody synthesized elsewhere) as the initiators, even if not the sole perpetuators of inflammation. The presence of autoantibodies to IgGFc, known as rheumatoid factors (RF), and antibodies to citrullinated peptides (ACPA) is an integral part of RA disease process. As is the case with many other autoimmune diseases, people with RA have abnormally glycosylated antibodies. It is believed that these glycan (oligosaccharide) alterations promote joint inflammation.
Once the abnormal immune response has become established (which may take several years before any symptoms occur), plasma cells derived from B lymphocytes produce rheumatoid factors and ACPA of the IgG and IgM classes in large quantities. These are not deposited in the way that they are in systemic lupus. Rather, they activate macrophages through Fc receptor and complement binding, which seems to play an important role in the intense inflammatory response present in RA. Binding of an autoreactive antibody to the Fc receptors is mediated through the antibody's N-glycans, which are altered to promote inflammation in people with RA. This contributes to inflammation of the synovium, in terms of edema, vasodilation and infiltration by activated T-cells (mainly CD4 in nodular aggregates and CD8 in diffuse infiltrates). Synovial macrophages and dendritic cells further function as antigen presenting cells by expressing MHC class II molecules, leading to an established local immune reaction in the tissue. The disease progresses in concert with the formation of granulation tissue at the edges of the synovial lining (pannus) with extensive angiogenesis and production of enzymes that cause tissue damage. Modern pharmacological treatments of RA target these mediators. Once the inflammatory reaction is established, the synovium thickens, the cartilage and the underlying bone begins to disintegrate and evidence of joint destruction accrues.
TNF (alpha) plays a major role in the pathogenesis of RA. There are several theories on how TNF release happens in disease process. If TNF release is stimulated by B cell products in the form of RF or ACPA -containing immune complexes, through activation of immunoglobulin Fc receptors, then RA can be seen as a form of Type III hypersensitivity. If TNF release is stimulated by T cell products such as interleukin-17 it might be considered closer to type IV hypersensitivity although this terminology may be getting somewhat dated and unhelpful.
Although TNF appears to be the dominant, other cytokines (chemical mediators) are likely to be involved in inflammation in RA. Blockade of TNF does not benefit all persons or all tissues (lung disease and nodules may get worse). Blockade of IL-1, IL-15 and IL-6 also have beneficial effects and IL-17 may be important. Constitutional symptoms such as fever, malaise, loss of appetite and weight loss are also caused by cytokines released into the blood stream. As with most autoimmune diseases, it is important to distinguish between the cause(s) that trigger the process and those that may permit it to persist and progress.
X-rays of the hands and feet are generally performed in people with many joints affected. In RA, there may be no changes in the early stages of the disease or the x-ray may demonstrate juxta-articular osteopenia, soft tissue swelling, and loss of joint space. As the disease advances, there may be bony erosions and subluxation. X-rays of other joints may be taken if symptoms of pain or swelling occur in those joints.
Other medical imaging techniques such as magnetic resonance imaging (MRI) and ultrasound are also used in RA.
There have been technical advances in ultrasonography. High-frequency transducers (10 MHz or higher) have improved the spatial resolution of ultrasound images; these images can depict 20% more erosions than conventional radiography. Also, color Doppler and power Doppler ultrasound, which show vascular signals of active synovitis depending on the degree of inflammation, are useful in assessing synovial inflammation. This is important, since in the early stages of RA, the synovium is primarily affected, and synovitis seems to be the best predictive marker of future joint damage.
When RA is clinically suspected, testing for the presence of rheumatoid factor (RF, a non-specific antibody) and ACPAs (measured as anti-CCP antibodies) may be required. A negative RF or CCP antibody does not rule out RA; rather, the arthritis is called seronegative. This is the case in about 15-25% of people with RA. During the first year of illness, rheumatoid factor is more likely to be negative with some individuals converting to seropositive status over time. RF is also seen in other illnesses, for example Sjögren's syndrome, hepatitis C, systemic lupus erythematosus, chronic infections and in approximately 10% of the healthy population, therefore the test is not very specific.
Because of this low specificity, new serological tests have been developed, which test for the presence of the anti-citrullinated protein antibodies (ACPAs) (clinically tested using the CCP assay). Like RF, these tests are positive in only a proportion (61-75%) of all RA cases, with a specificity of around 95%. As with RF, there is evidence for ACPAs being present in many cases even before onset of clinical disease.
The by far most common clinical test for ACPAs is the anti-CCP (cyclic citrullinated peptide) ELISA. Recently a serological point-of-care test (POCT) for the early detection of RA has been developed. This assay combines the detection of rheumatoid factor and anti-MCV for diagnosis of RA and shows a sensitivity of 72% and specificity of 99.7%.
Also, several other blood tests are usually done to allow for other causes of arthritis, such as lupus erythematosus. The erythrocyte sedimentation rate (ESR), C-reactive protein, full blood count, kidney function, liver enzymes and other immunological tests (e.g., antinuclear antibody/ANA) are all performed at this stage. Elevated ferritin levels can reveal hemochromatosis, a mimic of RA, or be a sign of Still's disease, a seronegative, usually juvenile, variant of rheumatoid arthritis.
In 2010 the 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria were introduced. The new criterion is not a diagnostic criterion but a classification criterion to identify disease with a high likelihood of developing a chronic form. However a score of 6 or greater unequivocally classifies a person with a diagnosis of rheumatoid arthritis.
These new classification criteria overruled the "old" ACR criteria of 1987 and are adapted for early RA diagnosis. The "new" classification criteria, jointly published by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) establish a point value between 0 and 10. Four areas are covered in the diagnosis:
The new criteria accommodate to the growing understanding of RA and the improvements in diagnosing RA and disease treatment. In the "new" criteria serology and autoimmune diagnostics carries major weight, as ACPA detection is appropriate to diagnose the disease in an early state, before joints destructions occur. Destruction of the joints viewed in radiological images was a significant point of the ACR criteria from 1987. This criterion no longer is regarded to be relevant, as this is just the type of damage that treatment is meant to avoid.
In clinical practice, the following criteria apply:
Several other medical conditions can resemble RA, and usually need to be distinguished from it at the time of diagnosis:
Rarer causes that usually behave differently but may cause joint pains:
Some patients are in a situation of undifferentiation (i.e. none of the above criteria is positive), even if synovitis is witnessed and assessed with ultrasound imaging.
There are many tools available for monitoring remission in rheumatoid arthritis.
From this, the disease activity of the affected person can be classified as follows:
One major limitation of use of the DAS28 score in clinical setting is low-grade synovitis may be missed.
There is no known prevention for the condition other than the reduction of risk factors.
There is no cure for RA, but treatments can improve symptoms and slow the progress of the disease. Disease-modifying treatment has the best results when it is started early and aggressively.
The goals of treatment are to minimize symptoms such as pain and swelling, to prevent bone deformity (for example, bone erosions visible in X-rays), and to maintain day-to-day functioning. This can often be achieved using two main classes of medications: analgesics such as NSAIDs, and disease-modifying antirheumatic drugs (DMARDs). RA should generally be treated with at least one specific anti-rheumatic medication. The use of benzodiazepines (such as diazepam) to treat the pain is not recommended as it does not appear to help and is associated with risks. Analgesics, other than NSAIDs, offer lesser, but some benefit with respect to pain whilst not causing the same level of gastrointestinal irritation.
Regular exercise is recommended as both safe and useful to maintain muscles strength and overall physical function. It is uncertain if specific dietary measures have an effect. Physical activity is beneficial for persons with Rheumatoid arthritis complaining of fatigue. Occupational therapy has a positive role to play in improving functional ability of persons with rheumatoid arthritis.
Disease modifying agents
Disease-modifying antirheumatic drugs (DMARDs) are the primary treatment for RA. They are a diverse collection of drugs, grouped by use and convention. They have been found to improve symptoms, decrease joint damage, and improve overall functional abilities. DMARDs should be started early in the disease as they result in disease remission in approximately half of people and improved outcomes overall.
The following drugs are considered as DMARDs: methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, TNF-alpha inhibitors (certolizumab, infliximab and etanercept), abatacept, and anakinra. Rituximab and tocilizumab are monoclonal antibodies and are also DMARDs.
The most commonly used agent is methotrexate with other frequently used agents including sulfasalazine and leflunomide. Sodium aurothiomalate (gold) and cyclosporin are less commonly used due to more common adverse effects. Agents may be used in combinations. Methotrexate is the most important and useful DMARD and is usually the first treatment. Adverse effects should be monitored regularly with toxicity including gastrointestinal, hematologic, pulmonary, and hepatic. Side effects such as nausea, vomiting or abdominal pain can be reduced by taking folic acid. The most common undesirable effect is that it increases liver enzymes in almost 15% of people. It is thus recommended that those who consistently demonstrate abnormal levels of liver enzymes or have a history of liver disease or alcohol use undergo liver biopsies.
A 2015 Cochrane review found rituximab with methotrexate to be effective in improving symptoms compared to methotrexate alone. Rituximab works by depicting levels of B-cells (immune cell that is involved in inflammation). People taking rituximab had improved pain, function, reduced disease activity and reduced joint damage based on x-ray images. After 6 months, 21% more people had improvement in their symptoms using rituximab and methotrexate.
Biological agents should generally only be used if methotrexate and other conventional agents are not effective after a trial of three months. They are associated with a higher rate of serious infections as compared to other DMARDs. These agents used to treat rheumatoid arthritis include: tumor necrosis factor alpha (TNFα) blockers such as infliximab; interleukin 1 blockers such as anakinra, monoclonal antibodies against B cells such as rituximab and tocilizumab, T cell costimulation blocker such as abatacept among others. They are often used in combination with either methotrexate or leflunomide. In those who are well controlled on TNF blockers decreasing the dose does not appear to affect overall function. Persons should be screened for latent tuberculosis before starting any TNF blockers therapy to avoid reactivation.
TNF blockers and methotrexate appear to have similar effectiveness when used alone and better results are obtained when used together. TNF blockers appear to have equivalent effectiveness with etanercept appearing to be the safest. Abatacept appears effective for RA with 20% more people improving with treatment than without but long term safety studies are yet unavailable. However, there is a lack of evidence to distinguish between the biologics available for RA. Issues with the biologics include their high cost and association with infections including tuberculosis.
NSAIDs reduce both pain and stiffness in those with RA. Generally they appear to have no effect on people's long term disease course and thus are no longer first line agents. NSAIDs should be used with caution in those with gastrointestinal, cardiovascular, or kidney problems. Use of methotrexate together with NSAIDS is safe, if adequate monitoring is done.
COX-2 inhibitors, such as celecoxib, and NSAIDs are equally effective. They have a similar gastrointestinal risk as an NSAIDs plus a proton pump inhibitor. In the elderly there is less gastrointestinal intolerance to celecoxib than to NSAIDs alone. There however is an increased risk of myocardial infarction with COX-2 inhibitors. Anti-ulcer medications are not recommended routinely but only in those high risk of gastrointestinal problems.
Glucocorticoids can be used in the short term for flare-ups, while waiting for slow-onset drugs to take effect. Injection of glucocorticoids into individual joints is also effective. While long-term use reduces joint damage it also results in osteoporosis and susceptibility to infections, and thus is not recommended.
In early phases of the disease, an arthroscopic or open synovectomy may be performed. It consists of the removal of the inflamed synovia and prevents a quick destruction of the affected joints. Severely affected joints may require joint replacement surgery, such as knee replacement. Postoperatively, physiotherapy is always necessary.
In general, there is not enough evidence to support any complementary health approaches for RA, with safety concerns for some of them. Some mind and body practices and dietary supplements may help people with symptoms and therefore may be beneficial additions to conventional treatments, but there is not enough evidence to draw conclusions. A systematic review of CAM modalities (excluding fish oil) found that " The available evidence does not support their current use in the management of RA.". Studies showing beneficial effects in RA on a wide variety of CAM modalities are often affected by publication bias and are generally not high quality evidence such as randomized controlled trials (RCTs).
A 2005 Cochrane review states that low level laser therapy can be tried to improve pain and morning stiffness due to rheumatoid arthritis as there are few side-effects.
There is some evidence that Tai Chi improves the range of motion of a joint in persons with rheumatoid arthritis. The evidence for acupuncture is inconclusive with it appearing to be equivalent to sham acupuncture.
Due to the false belief that herbal supplements are always safe, there is sometimes a hesitancy to report their use which may increase the risk of adverse reaction.
The following are under investigation for treatments for RA, based on preliminary promising results (not recommended for clinical use yet): boswellic acid, curcumin, devil's claw, Euonymus alatus, and thunder god vine (Tripterygium wilfordii). NCCIH has noted that, "In particular, the herb thunder god vine (Tripterygium wilfordii) can have serious side effects."
There is conflicting evidence on the role of erythropoiesis-stimulating agents for treatment of anemia in persons with rheumatoid arthritis.
More than 75% of women with rheumatoid arthritis have symptoms improve during pregnancy but might have symptoms worsen after delivery. Methotrexate and leflunomide are teratogenic (harmful to foetus) and not used in pregnancy. It is recommended women of childbearing age should use contraceptives to avoid pregnancy and to discontinue its use if pregnancy is planned. Low dose of prednisolone, hydroxychloroquine and sulfasalazine are considered safe in pregnant persons with rheumatoid arthritis.
People with RA have an increased risk of infections and mortality and recommended vaccinations can reduce these risks. The inactivated influenza vaccine should be received annually. The pneumococcal vaccine should be administered twice for people under the age 65 and once for those over 65. Lastly, the live-attenuated zoster vaccine should be administered once after the age 60, but is not recommended in people on a tumor necrosis factor alpha blocker.
The course of the disease varies greatly. Some people have mild short-term symptoms, but in most the disease is progressive for life. Around 20%–30% will have subcutaneous nodules (known as rheumatoid nodules); this is associated with a poor prognosis.
Poor prognostic factors include,
RA reduces lifespan on average from three to twelve years. According to the UK's National Rheumatoid Arthritis Society, Young age at onset, long disease duration, the concurrent presence of other health problems (called co-morbidity), and characteristics of severe RA—such as poor functional ability or overall health status, a lot of joint damage on x-rays, the need for hospitalisation or involvement of organs other than the joints—have been shown to associate with higher mortality". Positive responses to treatment may indicate a better prognosis. A 2005 study by the Mayo Clinic noted that RA sufferers suffer a doubled risk of heart disease, independent of other risk factors such as diabetes, alcohol abuse, and elevated cholesterol, blood pressure and body mass index. The mechanism by which RA causes this increased risk remains unknown; the presence of chronic inflammation has been proposed as a contributing factor. It is possible that the use of new biologic drug therapies extend the lifespan of people with RA and reduce the risk and progression of atherosclerosis. This is based on cohort and registry studies, and still remains hypothetical. It is still uncertain whether biologics improve vascular function in RA or not. There was an increase in total cholesterol and HDLc levels and no improvement of the atherogenic index.
RA affects between 0.5 and 1% of adults in the developed world with between 5 and 50 per 100,000 people newly developing the condition each year. In 2010 it resulted in about 49,000 deaths globally.
Onset is uncommon under the age of 15 and from then on the incidence rises with age until the age of 80. Women are affected three to five times as often as men.
The age at which the disease most commonly starts is in women between 40 and 50 years of age, and for men somewhat later. RA is a chronic disease, and although rarely, a spontaneous remission may occur, the natural course is almost invariably one of the persistent symptoms, waxing and waning in intensity, and a progressive deterioration of joint structures leading to deformations and disability.
The first known traces of arthritis date back at least as far as 4500 BC. A text dated 123 AD first describes symptoms very similar to RA. It was noted in skeletal remains of Native Americans found in Tennessee. In Europe, the disease is vanishingly rare before the 17th century. The first recognized description of RA in modern medicine was in 1800 by the French physician Dr Augustin Jacob Landré-Beauvais (1772–1840) who was based in the famed Salpêtrière Hospital in Paris. The name "rheumatoid arthritis" itself was coined in 1859 by British rheumatologist Dr Alfred Baring Garrod.
An anomaly has been noticed from the investigation of Pre-Columbian bones. The bones from the Tennessee site show no signs of tuberculosis even though it was prevalent at the time throughout the Americas.
The art of Peter Paul Rubens may possibly depict the effects of RA. In his later paintings, his rendered hands show, in the opinion of some physicians, increasing deformity consistent with the symptoms of the disease. RA appears to some to have been depicted in 16th-century paintings. However, it is generally recognized in art historical circles that the painting of hands in the 16th and 17th century followed certain stylized conventions, most clearly seen in the Mannerist movement. It was conventional, for instance, to show the upheld right hand of Christ in what now appears a deformed posture. These conventions are easily misinterpreted as portrayals of disease.
Historic treatments for RA have also included: rest, ice, compression and elevation, apple diet, nutmeg, some light exercise every now and then, nettles, bee venom, copper bracelets, rhubarb diet, extractions of teeth, fasting, honey, vitamins, insulin, magnets, and electroconvulsive therapy (ECT). The Prosorba column blood filtering device (removing IgG) was approved by the FDA in 1999 for treatment of RA However it was discontinued at the end of 2006.
Rheumatoid arthritis is derived from the Greek word ῥεύμα-rheuma (nom.), ῥεύματος-rheumatos (gen.) ("flow, current"). The suffix -oid ("resembling") gives the translation as joint inflammation that resembles rheumatic fever. Rhuma which means watery discharge might refer to the fact that the joints are swollen or that the disease may be made worse by wet weather.
The cause of RA has been a subject of intensive research.
One theory is that infections may provoke the autoimmune response characteristic of rheumatoid arthritis. One example of this theory is that unique bacterial species associated with periodontitis may initiate an autoimmune response in genetically susceptible individuals by citrullinating self-proteins, thus leading to the production of ACPAs. Meta-analysis found an association between periodontal disease and RA, but the mechanism of this association remains unclear.
Vitamin D deficiency is more common in people with rheumatoid arthritis than in the general population. However, whether vitamin D deficiency is a cause or a consequence of the disease remains unclear. 1α,25-dihydroxyvitamin D3 (1,25D), an active metabolite of vitamin D, affects bone metabolism indirectly through control of calcium and phosphate homeostasis. Interaction between 1,25D and the vitamin D receptor (VDR) affects the production of RANKL and delays osteoclastogenesis. Some trials have found a decreased risk for RA with vitamin D supplementation while others have not.