Rheumatoid Arthritis

Rheumatoid arthritis
Classification and external resources
A hand affected by rheumatoid arthritis
10	06
9	714
OMIM	180300
DiseasesDB	11506
MedlinePlus	000431
eMedicine	article/331715 article/1266195 article/305417 article/401271 article/335186 article/808419
MeSH	D001172

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease.

About 1% of the world’s population has rheumatoid arthritis, women three times more often than men. Onset is most frequent between the ages of 40 and 50, but people of any age can be affected. In addition, individuals with the HLA-DR1 or HLA-DR4 serotypes have an increased risk for developing the disorder. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated. It is a clinical diagnosis made on the basis of symptoms, physical exam, radiographs (X-rays) and labs, although the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) publish classification criteria for the purpose of research. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in joint, muscle and bone diseases.^[1]

Various treatments are available. Non-pharmacological treatment includes [3]

The name is based on the term “rheumatic fever“, an illness which includes joint pain and is derived from the Greek word ?????-rheuma (nom.), ????????-rheumatos (gen.) (“flow, current”). The suffix –oid (“resembling”) gives the translation as joint inflammation that resembles rheumatic fever. The first recognized description of rheumatoid arthritis was made in 1800 by Dr. Augustin Jacob Landré-Beauvais (1772–1840) of Paris.^[4]

Contents 1 Signs and symptoms 1.1 Joints 1.2 Skin 1.3 Lungs 1.4 Kidneys 1.5 Heart and blood vessels 1.6 Other 2 Diagnosis 2.1 Imaging 2.2 Blood tests 2.3 Criteria 2.4 Differential diagnoses 2.5 Monitoring progression 3 Causes 3.1 Genetics 3.2 Infectious triggers 3.3 Vitamin D 4 Pathophysiology 4.1 Abnormal immune response 5 Management 5.1 Disease modifying anti-rheumatic drugs 5.1.1 Traditional small molecular mass drugs 5.1.2 Biological agents 5.2 Anti-inflammatory agents and analgesics 5.3 Surgery 5.4 Other therapies 6 Prognosis 6.1 Prognostic factors 6.2 Mortality 7 Epidemiology 8 History 8.1 Notable cases 9 References 10 External links

[edit] Signs and symptoms

While rheumatoid arthritis primarily affects joints, problems involving other organs of the body are known to occur. Extra-articular (“outside the joints”) manifestations other than anemia (which is very common) are clinically evident in about 15–25% of individuals with rheumatoid arthritis.^[5] It can be difficult to determine whether disease manifestations are directly caused by the rheumatoid process itself, or from side effects of the medications commonly used to treat it – for example, lung fibrosis from methotrexate or osteoporosis from corticosteroids.

[edit] Joints

The arthritis of joints known as synovitis is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness limits their movement. With time RA nearly always affects multiple joints (it is a polyarthritis), most commonly 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.^[1]

Rheumatoid arthritis 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, often referred to as osteoarthritis or “wear-and-tear” arthritis. In arthritis of non-inflammatory causes, signs of inflammation and early morning stiffness are less prominent with stiffness typically less than 1 hour, and movements induce pain caused by mechanical arthritis.^[6] In RA, 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. Medical students are taught to learn names for specific deformities, such as swan neck deformity and “Z-thumb,” but these are of no more significance to diagnosis or disability than other variants, since they occur in osteoarthritis as well. “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.

[edit] Skin

The metacarpophalangeal joint, or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF (rheumatoid factor) titer and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on the body.

Several forms of livedo reticularis, which is a network (reticulum) of erythematous to purplish discoloration of the skin caused by the presence of an obliterative cutaneous capillaropathy.

Other, rather rare, skin associated symptoms include:

• pyoderma gangrenosum, a necrotizing, ulcerative, noninfectious neutrophilic dermatosis.
• Sweet’s syndrome, a neutrophilic dermatosis usually associated with myeloproliferative disorders
• drug reactions
• erythema nodosum
• lobular panniculitis
• atrophy of digital skin
• palmar erythema
• diffuse thinning (rice paper skin), and skin fragility (often worsened by corticosteroid use).

[edit] Lungs

Fibrosis of the lungs is a recognized response to rheumatoid disease. 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 rheumatoid arthritis and additional exposure to coal dust. Pleural effusions are also associated with rheumatoid arthritis. Another complication of RA is Rheumatoid Lung Disease. It is estimated that about one quarter of Americans with RA develop Rheumatoid Lung Disease.^[7]

[edit] Kidneys

Renal membranous nephropathy.

[edit] Heart and blood vessels

People with rheumatoid arthritis are more prone to [12]

[edit] Other

Ocular

The eye is directly affected in the form of nasolacrimal duct occlusion is important.

Hepatic

Cytokine production in joints and/or hepatic Felty’s syndrome, Kupffer cell activation is so marked that the resulting increase in hepatocyte activity is associated with nodular hyperplasia of the liver, which may be palpably enlarged. Although Kupffer cells are within the hepatic parenchyma, they are separate from hepatocytes. As a result there is little or no microscopic evidence of hepatitis (immune-mediated destruction of hepatocytes). Hepatic involvement in RA is essentially asymptomatic.

Hematological

Anemia is by far the most common abnormality of the blood cells. Rheumatoid arthritis may cause a warm autoimmune hemolytic anemia.^[13] The red cells are of normal size and colour (normocytic and normochromic). A low white blood cell count (neutropenia) usually only occurs in patients with Felty’s syndrome with an enlarged liver and spleen. The mechanism of neutropenia is complex. An increased platelet count (thrombocytosis) occurs when inflammation is uncontrolled, as does the anemia.

Neurological

quadriplegia.

Constitutional symptoms

loss of weight are common systemic manifestations seen in patients with active rheumatoid arthritis.

Osteoporosis

Local osteoporosis occurs in RA around inflamed joints. It is postulated to be partially caused by inflammatory cytokines. More general osteoporosis is probably contributed to by immobility, systemic cytokine effects, local cytokine release in bone marrow and corticosteroid therapy.

Lymphoma

The incidence of [15]

[edit] Diagnosis

[edit] Imaging

X-ray of the hand in rheumatoid arthritis.

Appearance of synovial fluid from a joint with inflammatory arthritis.

Signs of destruction and inflammation on synovitis. Ultrasonography (left side of image) in the (a) longitudinal and (b) the transverse planes shows both signs of destruction and inflammation. Axial T1-weighted magnetic resonance images were obtained (c) before and (d) after contrast administration, also demonstrating synovitis. Additionally, a coronal T1-weighted magnetic resonance image (e) before contrast administration visualizes the same bone erosion as shown in panels c and d.

X-rays of the hands and feet are generally performed in people with a polyarthritis. In rheumatoid arthritis, 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 rheumatoid arthritis.^{[citation needed]}

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 rheumatoid arthritis, the synovium is primarily affected, and synovitis seems to be the best predictive marker of future joint damage.^[16]

[edit] Blood tests

When RA is clinically suspected, Sjögren’s syndrome, Hepatitis C, 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) or anti-CCP. Like RF, these tests are positive in only a proportion (67%) of all RA cases, but are rarely positive if RA is not present, giving it a specificity of around 95%.^[18] As with RF, there is evidence for ACPAs being present in many cases even before onset of clinical disease.^{[citation needed]}

The most common tests for ACPAs are the anti-CCP ([20]

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, renal 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 RA, or be a sign of Still’s disease ^{[disambiguation needed]}, a seronegative, usually juvenile, variant of rheumatoid.^{[citation needed]}

[edit] Criteria

In 2010 the 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria were introduced.^[21]

• joint involvement, designating the ankles as large joints:
  • Involvement of 1 large joint gives 0 points
  • Involvement of 2-10 large joints gives 1 point
  • Involvement of 1-3 small joints (with or without involvement of large joints) gives 2 points
  • Involvement of 4-10 small joints (with or without involvement of large joints) gives 3 points
  • Involvement of more than 10 joints (with involvement of at least 1 small joint) gives 5 points
• serological parameters – including the ACPA – “ACPA” stands for “anti-citrullinated protein antibody”:
  • Negative RF and negative ACPA gives 0 points
  • Low-positive RF or low-positive ACPA gives 2 points
  • High-positive RF or high-positive ACPA gives 3 points
• acute phase reactants: 1 point for elevated erythrocyte sedimentation rate, CRP value (c-reactive protein)
• duration of arthritis: 1 point for symptoms lasting six weeks or longer

The new criteria accommodate to the growing understanding of rheumatoid arthritis 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.^[22] This criterion no longer is regarded to be relevant, as this is just the type of damage that treatment is meant to avoid.

The criteria are not intended for the diagnosis for routine clinical care; they were primarily intended to categorize research (classification criteria). In clinical practice, the following criteria apply:^{[citation needed]}

• two or more swollen joints
• morning stiffness lasting more than one hour for at least six weeks
• the detection of mutated citrullinated vimentin can confirm the suspicion of rheumatoid arthritis. A negative autoantibody result does not exclude a diagnosis of RA.

[edit] Differential diagnoses

Several other medical conditions can resemble RA, and usually need to be distinguished from it at the time of diagnosis:^[24]

• Crystal induced arthritis (pseudogout) – usually involves particular joints (knee, MTP1, heels) and can be distinguished with aspiration of joint fluid if in doubt. Redness, asymmetric distribution of affected joints, pain occurs at night and the starting pain is less than an hour with gout.
• Osteoarthritis – distinguished with X-rays of the affected joints and blood tests, age (mostly older patients), starting pain less than an hour, a-symmetric distribution of affected joints and pain worsens when using joint for longer periods.
• Systemic lupus erythematosus (SLE) – distinguished by specific clinical symptoms and blood tests (antibodies against double-stranded DNA)
• One of the several types of psoriatic arthritis resembles RA – nail changes and skin symptoms distinguish between them
• Lyme disease causes erosive arthritis and may closely resemble RA – it may be distinguished by blood test in endemic areas
• keratoderma blennorrhagica.
• Ankylosing spondylitis – this involves the spine, although a RA-like symmetrical small-joint polyarthritis may occur in the context of this condition.
• Hepatitis C – RA-like symmetrical small-joint polyarthritis may occur in the context of this condition. Hepatitis C may also induce Rheumatoid Factor auto-antibodies

Rarer causes that usually behave differently but may cause joint pains:^[23]

• Whipple’s disease can also resemble RA.
• Hemochromatosis may cause hand joint arthritis.
• Acute rheumatic fever can be differentiated from RA by a migratory pattern of joint involvement and evidence of antecedent streptococcal infection. Bacterial arthritis (such as streptococcus) is usually asymmetric, while RA usually involves both sides of the body symmetrically.
• tendons around the wrists and ankles.

[edit] Monitoring progression

The progression of rheumatoid arthritis can be followed using scores such as Disease Activity Score of 28 joints (DAS28). It is widely used as an indicator of RA disease activity and response to treatment, but is not always a reliable indicator of treatment effect.^[26]

From this, the disease activity of the patient can be classified as follows:^[26]

Current DAS28		DAS28 decrease from initial value
		> 1.2	> 0.6 but ? 1.2	? 0.6
? 3.2	Inactive	Good improvement	Moderate improvement	No improvement
> 3.2 but ? 5.1	Moderate	Moderate improvement	Moderate improvement	No improvement
> 5.1	Very active	Moderate improvement	No improvement	No improvement

[edit] Causes

Rheumatoid arthritis is a form of autoimmunity, the causes of which are still not completely known. 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^[27]

[edit] Genetics

It is strongly associated with the inherited tissue type citation needed]

[edit] Infectious triggers

It has long been suspected that certain infections could be triggers for this disease. The “mistaken identity” theory suggests that an infection triggers an immune response, leaving behind antibodies that should be specific to that organism. The antibodies are not sufficiently specific, though, and set off an immune attack against part of the host. Because the normal host molecule “looks like” a molecule on the offending organism that triggered the initial immune reaction—this phenomenon is called rubella, but these associations have never been supported in epidemiological studies. Nor has convincing evidence been presented for other types of triggers such as food allergies.

Epidemiological studies have confirmed a potential association between RA and two [31]

[edit] Vitamin D

The discovery of the vitamin D receptor (VDR) in the cells of the immune system and the fact that activated dendritic cells produce the vitamin D hormone suggested that [33]

It is too early to tell whether administering vitamin D directly affects disease activity.^[34]

[edit] Pathophysiology

The key pieces of evidence relating to pathogenesis are:

1. A genetic link with PTPN22.
2. An undeniable link to the pathogenesis of vascular disease of many types, including the possibility of a strong causal connection to rheumatoid vasculitis, a typical feature of this condition.^[35]
3. A remarkable deceleration of disease progression in many cases by blockade of the cytokine TNF (alpha).
4. A similar dramatic response in many cases to depletion of T lymphocytes.
5. A more or less random pattern of whether and when predisposed individuals are affected.
6. The presence of autoantibodies to IgGFc, known as antibodies to citrullinated peptides (ACPA).

These data suggest that the disease involves abnormal B cell–T cell interaction, with presentation of antigens by B cells to T cells via HLA-DR eliciting T cell help and consequent production of RF and ACPA. Inflammation is then driven either by B cell or T cell products stimulating release of TNF and other cytokines. The process may be facilitated by an effect of smoking on autoimmunity for general mechanisms.)

If TNF release is stimulated by B cell products in the form of RF or ACPA -containing immune complexes, through activation of immunoglobulin citation needed]

Although TNF appears to be the dominant, other IL-17 may be important. Constitutional symptoms such as fever, malaise, loss of appetite and weight loss are also caused by cytokines released in to 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.

[edit] Abnormal immune response

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 autoimmunity).

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 appear to activate macrophages through Fc receptor and perhaps complement binding. This can contribute 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 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.

[edit] Management

There is no known cure for rheumatoid arthritis, but many different types of treatment can alleviate symptoms and/or modify the disease process. Recommendations of the American College of Rheumatology (ACR), published in 2008, followed a trend in supporting earlier, more aggressive treatment of RA, and reflected heightened expectations of treatment effectiveness, including remission or substantial alleviation of symptoms for a rising percentage of patients.^[42]

The goals of treatment include minimizing clinical symptoms such as pain and swelling, as well as preventing bone deformity and radiographic damage (for example, bone erosions visible in X-rays), and maintaining the quality of life in terms of day-to-day activities.^[42]

citation needed]

[47] Treatment also includes rest and physical activity.

[edit] Disease modifying anti-rheumatic drugs

This section needs additional citations for verification. (October 2008)

The term Disease-modifying anti-rheumatic drug (DMARD) originally meant a drug that affects biological measures such as ESR and haemoglobin and autoantibody levels, but is now usually used to mean a drug that reduces the rate of damage to bone and cartilage. DMARDs have been found both to produce durable symptomatic remissions and to delay or halt progression. This is important as such damage is usually irreversible. Anti-inflammatories and analgesics improve pain and stiffness but do not prevent joint damage or slow the disease progression.

There is an increasing recognition among rheumatologists that permanent damage to the joints occurs at a very early stage in the disease. In the past it was common to start with just an anti-inflammatory drug, and assess progression clinically and using X-rays. If there was evidence that joint damage was starting to occur then a more potent DMARD would be prescribed. Ultrasound and MRI are more sensitive methods of imaging the joints and have demonstrated that joint damage occurs much earlier and in more sufferers than was previously thought. People with normal X-rays will often have erosions detectable by ultrasound that X-rays could not demonstrate. The aim now is to treat before damage occurs.

There may be other reasons why starting DMARDs early is beneficial as well as prevention of structural joint damage. From the earliest stages of the disease, the joints are infiltrated by cells of the immune system that signal to one another in ways that may involve a variety of positive feedback loops (it has long been observed that a single corticosteroid injection may abort synovitis in a particular joint for long periods). Interrupting this process as early as possible with an effective DMARD (such as methotrexate) appears to improve the outcome from the RA for years afterwards. Delaying therapy for as little as a few months after the onset of symptoms can result in worse outcomes in the long term. There is therefore considerable interest in establishing the most effective therapy with early arthritis, when they are most responsive to therapy and have the most to gain.^[48]

Disease-modifying anti-rheumatic drugs have been used in the treatment of rheumatic arthritis for a long time now. Over 90% of rheumatologists now use combination therapy of multiple disease modifying drugs for rheumatoid arthritis as it has become apparent that using combination of these drugs does not increase their relative toxicity profiles.^[49] Common combinations of DMARDs include methotrexate – hydroxychloroquine, methotrexate – sulfasalazine, sulfasalazine – hydroxychloroquine, and methotrexate – hydroxychloroquine – sulfasalazine.

In order to be effective, disease-modifying anti-rheumatic drugs must be administered before the deformities appear or the erosive disease occurs. Usually, Rheumatologists do not wait for the fulfillment of the criteria for classification of RA as published by the American College of Rheumatology (ACR) and start treatment with this type of drugs if the pain and synovitis persist and the function is compromised.^[50]

[edit] Traditional small molecular mass drugs

Chemically synthesised DMARDs:

Cytotoxic drugs:

• Cyclophosphamide

The most important and most common adverse events relate to bone marrow toxicity (MTX, SSZ, leflunomide, azathioprine, gold compounds, D-penicillamine), renal toxicity (cyclosporine A, parenteral gold salts, D-penicillamine), pneumonitis (MTX), allergic skin reactions (gold compounds, SSZ), autoimmunity (D-penicillamine, SSZ, minocycline) and infections (azathioprine, cyclosporine A).

Hydroxychloroquine may cause ocular toxicity, although this is rare, and because hydroxychloroquine does not affect the bone marrow or liver it is often considered to be the DMARD with the least toxicity. Unfortunately hydroxychloroquine is not very potent, and is usually insufficient to control symptoms on its own.^{[citation needed]}

Methotrexate is considered by many rheumatologists to be the most important and useful DMARD and is often part of the initial line of treatment.^[51]

In clinical trials, where one of a range of different DMARDs were used, people who were prescribed methotrexate stayed on their medication the longest (the others stopped because of either side-effects or failure of the drug to control the arthritis).^{[citation needed]} Methotrexate is often preferred by rheumatologists because if it does not control arthritis on its own then it works well in combination with many other drugs, especially the biological agents. Other DMARDs may not be as effective or as safe in combination with biological agents.^{[citation needed]}

Sulphasalazine : Although it appears to be a highly efficient drug in the treatment of rheumatoid arthritis, sulphasalazine may cause side effects that can range in severity from mild to serious. Mild side effects that may arise from treatment with sulphasalazine include Leukopenia has also been reported in therapies with sulphasalazine, but in very rare cases.

Anti-malarials such as chloroquine and hydroxychloroquine have been used to treat rheumatoid arthritis. It has been pointed out, through clinical studies, that chloroquine has a higher toxicity compared to hydroxychloroquine. Although hydroxyxhloroquine appears to be more efficient in treating rheumatoid arthritis than placebo, it is also inferior to sulphasalazine, especially in what concerns preventing the joint damage that is caused by the disease. As with most drugs, anti-malarials may also produce side effects. Mild side effects from hydroxychloroquine include nausea and skin rash. More serious, bone marrow suppression may occur, though rare. Also, aplastic anemia and agranulocytosis can develop as a result of anti-malarial therapy and may potentially cause the death of the patient. A much more worrisome side effect from treatment with anti-malarials is the damage that these drugs may cause to the cornea and retina. Recent studies have shown that if the dosage of hydroxychloroquine given to the patients does not exceed 6.5 mg/kg, the risks of developing ocular complications are minimal.^[53]

auranofin. Yet, this type of drug has been shown to be more efficient than placebo and even though its level of toxicity is quite low, auranofin seems to be causing more side effects than any other type of DMARD. Auranofin is therefore not considered efficient in the treatment of rheumatoid arthritis because of its poor results and because it is intolerable for most patients. Sodium aurothiomalate (Myocrisin) on the other hand is another type of gold compound that is injected and which appears to be as efficient as sulphasalazine, d-penicillamine and methotrexate. Given that there is not enough proof that gold compounds are indeed efficient in preventing the progression of erosions and the high toxicity of these drugs, they are usually not included in the treatment plan for rheumatoid arthritis.

A Cochrane systematic review has determined that [55]

[edit] Biological agents

Biological agents (biologics) include:

• golimumab (Simponi)
• anakinra (Kineret)
• monoclonal antibodies against B cells – rituximab (Rituxan)^[59]
• abatacept (Orencia)
• tocilizumab (an anti-IL-6 receptor antibody) (RoActemra, Actemra)

[edit] Anti-inflammatory agents and analgesics

Anti-inflammatory agents include: non-steroidal anti-inflammatory drug

Analgesics include: lidocaine topical

Cortisone therapy became a controversial medical solution because even though it can provide great relief, there are some questions as to the usefulness of the procedure over a long period of time.^[60]

There is some evidence that daily consumption of [62]

[edit] Surgery

In early phases of the disease, an arthroscopic or open physiotherapy is always necessary.

[edit] Other therapies

Regular exercise is important for maintaining joint mobility and making the joint muscles stronger. A Cochrane Review of studies determined that exercise programs designed to improve strength and stamina were safe and led to moderate benefits for RA sufferers.^[63]

Other therapies are joint injections, and special tools to improve hand movements (e.g., special tin-openers).

The [65]

The effectiveness of treating RA with acupuncture is inconclusive.^[66]

[edit] Prognosis

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.

[edit] Prognostic factors

Poor prognostic factors include persistent synovitis, early erosive disease,extra-articular findings (including subcutaneous rheumatoid nodules), positive serum RF findings, positive serum anti-CCP autoantibodies, carriership of HLA-DR4 “Shared Epitope” alleles, family history of RA, poor functional status, socioeconomic factors, elevated acute phase response (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and increased clinical severity.

[edit] Mortality

RA is known to reduce the lifespan of patients by anywhere from three to 12 years.^[70]

[edit] Epidemiology

The [75]

The risk of first developing the disease (the disease incidence) appears to be greatest for women between 40 and 50 years of age, and for men somewhat later.^[76] RA is a chronic disease, and although rarely, a spontaneous remission may occur, the natural course is almost invariably one of persistent symptoms, waxing and waning in intensity, and a progressive deterioration of joint structures leading to deformations and disability.

[edit] History

The first known traces of arthritis date back at least as far as 4500 BC. A text dated Age of Exploration. In 1859 the disease acquired its current name.

An anomaly has been noticed from investigation of Precolumbian bones. The bones from the Tennessee site show no signs of tuberculosis even though it was prevalent at the time throughout the Americas.^[80] Mobley attributes the spikes in arthritis to selective pressure caused by tuberculosis. A hypervigilant immune system is protective against tuberculosis at the cost of an increased risk of autoimmune disease.

The art of [83] However, it is generally recognised in art historical circles that the painting of hands in the 16th and 17th century followed certain stylised 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. They are much too widespread for this to be plausible.

The first recognized description of rheumatoid arthritis was in 1800 by the French physician Dr Augustin Jacob Landré-Beauvais (1772–1840) who was based in the famed [84]

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).^[85] Most of these have either had no effect at all, or their effects have been modest and transient, while not being generalizable.^{[citation needed]}

[edit] Notable cases

• Christiaan Barnard, the first surgeon to perform a human-to-human heart transplant had to retire owing to the condition. He also wrote a book on living with arthritis.
• Billy Bowden, international cricket umpire who had to retire from active play because of rheumatoid arthritis.
• Anita Carter, country music singer, daughter of Maybelle Carter.
• James Coburn claimed to have healed the condition using pills containing a sulfur-containing compound on his return to acting.
• Raoul Dufy, French artist (1877–1953), continued to paint despite RA and was one of the first patients ever treated with cortisone, in a Boston hospital.
• M*A*S*H.
• Melvin Franklin, bass singer of the Temptations. He treated RA with cortisone shots so he could perform.
• genetic code.
• Matt Iseman, licensed physician and professional comedian, and host of Style Network’s Clean House.
• Sandy Koufax, an American Hall-of-Fame baseball pitcher who played from 1955 to 1966 for the Los Angeles Dodgers.
• Erik Lindbergh, aviator and member of the X-Prize administration. Erik has been a spokesman for the arthritis drug Enbrel, as a result of his success with the treatment.^[86]
• Bob Mortimer British comedian and actor.^[87]
• Auguste Renoir, impressionist painter, whose later ‘softer’ style might have reflected in some way his severe disability.
• Kathleen Turner and Aida Turturro have worked to raise public awareness of the condition^[88]
• Theodore Roosevelt, president of the United States, had his lung arthritis act up for the rest of his life, after the assassination attempt on him, giving a speech with a bullet lodged in his body.

[edit] References

[edit] External links

Wikimedia Commons has media related to: Rheumatoid arthritis

• “Within Our Reach: Finding a Cure for Rheumatoid Arthritis”. American College of Rheumatology Research and Education Foundation. http://www.withinourreach.info.
• Rheumatoid arthritis at the Open Directory Project
• “Rheumatoid Arthritis”. Arthritis Foundation. http://www.arthritis.org/conditions/DiseaseCenter/RA/default.asp.
• “Rheumatoid Arthritis”. Arthritis Research Campaign. http://www.arc.org.uk/arthinfo/patpubs/6033/6033.asp.
• Charles Weber. “History of rheumatoid arthritis”. http://charles_w.tripod.com/arthritis2.html.
• “Rheumatoid Arthritis Details”. NIH Senior Health. http://nihseniorhealth.gov/rheumatoidarthritis/toc.html.
• “National Institute of Arthritis and Musculoskeletal and Skin Diseases”. National Institute of Arthritis and Musculoskeletal and Skin Diseases. http://www.niams.nih.gov/.
• “Arthritis Related Statistics”. Centers for Disease Control and Prevention (CDC). http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm.
• “Rheumatoid Arthritis”. MedlinePlus. http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html.

v t e 711–719) Arthritis (monoarthritis / polyarthritis) Inflammation (Neutrophilia) Infectious Septic arthritis Tuberculosis arthritis Reactive arthritis (indirectly) Noninfectious Seronegative spondyloarthropathy: Reactive arthritis Psoriatic arthritis Ankylosing spondylitis Rheumatoid arthritis: Juvenile idiopathic arthritis Adult-onset Still’s disease Felty’s syndrome Gout Chondrocalcinosis Noninflammatory Heberden’s node Bouchard’s nodes Other hemorrhage Hemarthrosis pain Arthralgia Osteophyte villonodular synovitis Pigmented villonodular synovitis Joint stiffness JNT phys noco(injr M4)

v t e 279.5–6) atopy (IgE) Foreign Penicillin allergy Autoimmune none ADCC (IgG) Foreign Pernicious anemia · Hemolytic disease of the newborn Autoimmune Cytotoxic Goodpasture’s syndrome “Type 5“/receptor Graves’ disease · Myasthenia gravis Type III (Immune complex) Foreign Henoch–Schönlein purpura · Hypersensitivity vasculitis · Reactive arthritis · Farmer’s lung · Post-streptococcal glomerulonephritis · Serum sickness · Arthus reaction Autoimmune Systemic lupus erythematosus · Subacute bacterial endocarditis · Rheumatoid arthritis cell-mediated (T-cells) Foreign Allergic contact dermatitis · Mantoux test Autoimmune Giant-cell arteritis GVHD Transfusion-associated graft versus host disease Unknown/ multiple Foreign Latex allergy (I+IV) Autoimmune Systemic autoimmune disease LMC igrc tumr 4)

This article uses material from the Wikipedia article Rheumatoid Arthritis, which is released under the Creative Commons Attribution-Share-Alike License 3.0.