Rheumatoid arthritis
From Wikipedia, the free encyclopedia
Rheumatoid arthritis
A hand affected by rheumatoid arthritis
Classification and external resources
Specialty
Rheumatology
ICD-10
M05-M06
ICD-9-CM
714
OMIM
180300
DiseasesDB
11506
MedlinePlus 000431
eMedicine
article/331715article/1266195article/305417article/401271article/335186article/808419
Patient UK
Rheumatoid arthritis
MeSH
D001172
Rheumatoid arthritis (RA) is a long lasting 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 typically the same joints involved on
both sides of the body. The disease may also affect other parts of the body. This may result
in low red blood cells, inflammation around the lungs, and inflammation around the heart. Fever
and low energy may also be present.[1] Often symptoms come on gradually over weeks to
months.[2]
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.[1] The diagnosis is made mostly on the basis of a
person's signs and symptoms.[2] X-rays and laboratory testing may support a diagnosis or
exclude other diseases with similar symptoms.[1] Other diseases that may present similarly
include systemic lupus erythematosus, psoriatic arthritis, and fibromyalgia among others.[2]
The goal of treatment is to improve 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 calleddisease-modifying antirheumatic drugs (DMARDs)
may be used to try to slow the progression of disease. They include the
medications hydroxychloroquine and methotrexate.[1] Biological DMARDs may be used when
disease does not respond to other treatments.[3] However, they may have a greater rate of
adverse effects.[4] Surgery to repair, replace, or fusion joints may help in certain
situations.[1] Most alternative medicine treatments are not supported by evidence.[5][6]
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.[3] Onset is most frequent during middle
age and women are affected 2.5 times as frequently as men.[1] In 2013 it resulted in 38,000
deaths up from 28,000 deaths in 1990.[7] The first recognized description of RA was made in
1800 by Dr. Augustin Jacob Landré-Beauvais (1772–1840) of Paris.[8]The term rheumatoid
arthritis is based on the Greek for watery and inflamed joints.[9]
Contents
[hide]







1Signs and symptoms
o 1.1Joints
o 1.2Skin
o 1.3Lungs
o 1.4Kidneys
o 1.5Heart and blood vessels
o 1.6Other
2Causes
3Pathophysiology
4Diagnosis
o 4.1Imaging
o 4.2Blood tests
o 4.3Classification Criteria
o 4.4Differential diagnoses
o 4.5Monitoring progression
5Prevention
6Management
o 6.1Lifestyle
o 6.2Disease modifying agents
o 6.3Anti-inflammatory agents
o 6.4Surgery
o 6.5Alternative medicine
o 6.6Pregnancy
o 6.7Vaccinations
7Prognosis
o 7.1Prognostic factors




o 7.2Mortality
8Epidemiology
9History
o 9.1Etymology
10References
11External links
Signs and symptoms[edit]
RA primarily affects joints, however it also affects other organs in more than 15–25% of
individuals.[10]
Joints[edit]
A diagram showing how rheumatoid arthritis affects a joint
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 (it is
a 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.[11]:1089 Synovitis can lead
to tethering of tissue with loss of movement and erosion of the joint surface causing deformity
and loss of function.[2]
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,
often referred to 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.[12] The pain associated with RA is
induced at the site of inflammation and classified as nociceptiveas opposed
to neuropathic.[13] The joints are often affected in a fairly symmetrical fashion, although this is not
specific, and the initial presentation may be asymmetrical.[11]:1089
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, swan neck deformity and "Z-thumb." "Z-thumb" or "Z-deformity" consists
ofhyperextension of the interphalangeal joint, fixed flexion and subluxation of
the metacarpophalangeal joint and gives a "Z" appearance to the thumb.[11]:1089 The hammer
toe deformity may be seen. In the worst case, joints are known asarthritis mutilans due to the
mutilating nature of the deformities.[14]
Skin[edit]
The rheumatoid nodule, which is sometimes in the skin, is the most common non joint
feature.[15] They occur in 30% of people.[15] 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 thesubintimal 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 and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse
sites on the body.[citation needed].
Several forms of vasculitis occur in RA. A benign form occurs as microinfarcts around
the nailfolds. More severe forms include livedo reticularis, which is a network (reticulum)
of erythematous to purplish discoloration of the skin caused by the presence of an obliterative
cutaneous capillaropathy.[citation needed].
Other, rather rare, skin associated symptoms include pyoderma gangrenosum, Sweet's
syndrome, drug reactions, erythema nodosum, lobe panniculitis,atrophy of finger skin, palmar
erythema, diffuse thinning (rice paper skin), and skin fragility (often worsened by corticosteroid
use).[citation needed].
Lungs[edit]
Fibrosis of the lungs is a recognized response to rheumatoid disease. It is also a rare but well
recognized consequence of therapy (for example withmethotrexate and leflunomide). Caplan's
syndrome describes lung nodules in individuals with RA and additional exposure
to coal dust. Pleural effusions are also associated with RA. Another complication of RA
is Rheumatoid Lung Disease. It is estimated that about one quarter of Americans with RA
develop Rheumatoid Lung Disease.[16]
Kidneys[edit]
Renal amyloidosis can occur as a consequence of chronic inflammation.[17] RA may affect the
kidney glomerulus directly through a vasculopathy or amesangial infiltrate but this is less well
documented (though this is not surprising, considering immune complex-mediated
hypersensitivities are known forpathogenic deposition of immune complexes in organs where
blood is filtered at high pressure to form other fluids, such as urine and synovial fluid[18]).
Treatment with penicillamine and gold salts are recognized causes of membranous nephropathy.
Heart and blood vessels[edit]
People with RA are more prone to atherosclerosis, and risk of myocardial infarction (heart attack)
and stroke is markedly increased.[19][20] Other possible complications that may arise
include: pericarditis, endocarditis, left ventricular failure, valvulitis and fibrosis.[21] 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
theinflammation 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.[21]
Other[edit]
Eyes
The eye is directly affected in the form of episcleritis which when severe can very rarely
progress to perforating scleromalacia. Rather more common is the indirect effect
of keratoconjunctivitis sicca, which is a dryness of eyes and mouth caused
by lymphocyte infiltration of lacrimal and salivary glands. When severe, dryness of the
cornea can lead to keratitis and loss of vision. Preventive treatment of severe dryness
with measures such as nasolacrimal ductblockage is important.
Liver
Liver problems in people with rheumatoid arthritis may be due to the underlying disease
process or as a result of the medications used to treat the disease.[22] A coexisting
autoimmune liver disease, such as primary biliary cirrhosis or autoimmune hepatitis may
also cause problems.[22]
Blood
Anemia is by far the most common abnormality of the blood cells which can be caused
by a variety of mechanisms. The chronic inflammation caused by RA leads to
raised hepcidin levels, leading to anemia of chronic disease where iron is poorly
absorbed and also sequestered into macrophages. RA may also cause a warm
autoimmune hemolytic anemia.[23] The red cells are of normal size and colour (normocytic
and normochromic). A low white blood cell countusually only occurs in people with Felty's
syndrome with an enlarged liver and spleen. The mechanism of neutropenia is complex.
An increased platelet count occurs when inflammation is uncontrolled.
Neurological
Peripheral neuropathy and mononeuritis multiplex may occur. The most common
problem is carpal tunnel syndrome caused by compression of the median nerve by
swelling around the wrist. Atlanto-axial subluxation can occur, owing to erosion of
the odontoid process and/or transverse ligaments in the cervical spine's connection to the
skull. Such an erosion (>3mm) can give rise to vertebrae slipping over one another and
compressing the spinal cord. Clumsiness is initially experienced, but without due care
this can progress to quadriplegia.
Constitutional symptoms
Constitutional symptoms including fatigue, low grade fever, malaise, morning
stiffness, loss of appetite and loss of weight are common systemic manifestations seen in
people with active RA.
Bones
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.
Cancer
The incidence of lymphoma is increased in RA, although it is uncommon.[24][25]
Causes[edit]
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.[26]
Half of the risk for RA is believed to be genetic.[3] 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 born 0404), and the genes
PTPN22 and PADI4—hence family history is an important risk
factor.[27][28] Inheriting the PTPN22 gene has been shown to double a
person's susceptibility to RA. PADI4 has been identified as a major
risk factor in people of Asian descent, but not in those of European
descent.[29] First-degree relatives prevalence rate is 2–3% and
disease genetic concordance inmonozygotic twins is approximately
15–20%.[30][31]
Smoking is the most significant non-genetic risk[3] 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.[32] Modest alcohol consumption may be protective.[33]
Epidemiological studies have confirmed a potential association
between RA and two herpesvirus infections: Epstein-Barr
virus (EBV) and Human Herpes Virus 6 (HHV-6).[34] Individuals with
RA are more likely to exhibit an abnormal immune response to EBV
and have high levels of anti-EBV antibodies.[35]
Vitamin D deficiency is more common in people with rheumatoid
arthritis than in the general population.[36][37] However, whether
vitamin D deficiency is a cause or a consequence of the disease
remains unclear.[38] 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.[39] Some trials have found a
decreased risk for RA with vitamin D supplementation while others
have not.[37]
Pathophysiology[edit]
Both genetic as well as environmental factors are implicated in the
pathophysiology of the disease. Smoking is the main environmental
risk to RA.[3] 50% of the risk of having RA is attributable to genetic
factors.[3] No infectious agent has been consistently linked with RA
and there is no evidence of disease clustering to indicate its
infectious etiology.[40] HLA-DR4 is the major genetic factor implicated
- but its relative importance varies across ethnic
groups.[40][41] Related allotypes of MHC Class II and the T cellassociated protein PTPN22 has also been found associated in
many studies.[41]
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:[14]

Initiation phase, due to non-specific inflammation.


Amplification phase, due to T cell activation
Chronic inflammatory phase with tissue injury, due
to cytokines IL–1, TNF-alpha and IL–6.
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,[41] 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.[32][42] 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
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 synthesised
elsewhere) as the initiators, even if not the sole perpetuators of
inflammation.[citation needed]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.[43] It is believed that these
glycan (oligosaccharide) alterations promote joint inflammation.[43]
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.[44] Binding of an autoreactive
antibody to the Fc receptors is mediated through the antibody's Nglycans, which are altered to promote inflammation in people with
RA.[43] 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 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.[45][46] 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.[47]
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.[citation needed] 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.[citation
needed]
Diagnosis[edit]
Imaging[edit]
X-ray of the hand in rheumatoid arthritis.
Appearance of synovial fluid from a joint with inflammatory arthritis.
Signs of destruction and inflammation on ultrasonography andmagnetic
resonance imaging in the second metacarpophalangeal joint in
established RA. Thin arrows indicate an erosive change; thick arrows
indicate 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 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. Xrays 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.[14]
There have been technical advances in ultrasonography. Highfrequency 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.[48]
Blood tests[edit]
When RA is clinically suspected, testing for the presence
of rheumatoid factor (RF, a non-specific antibody) and (ACPAs)
may be required.[49] A negative RF does not rule out RA; rather, the
arthritis is called seronegative. This is the case in about 15% of
people with RA.[50][51] 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.[14]
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%.[50] As with RF, there is evidence for ACPAs being present in
many cases even before onset of clinical disease.[14]
The most common tests for ACPAs are the anti-CCP (cyclic
citrullinated peptide) test and the Anti-MCV assay (antibodies
against mutated citrullinated Vimentin). Recently a serological pointof-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%.[52][53]
Also, several other blood tests are usually done to allow for other
causes of arthritis, such as lupus erythematosus. Theerythrocyte
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 revealhemochromatosis, a mimic of RA,
or be a sign of Still's disease, a seronegative, usually juvenile,
variant of rheumatoid arthritis.[citation needed]
Classification Criteria[edit]
In 2010 the 2010 ACR / EULAR Rheumatoid Arthritis Classification
Criteria were introduced.[54][55] The new criterion is not a diagnostic
criterion but a classification criterion to identify disease with a high
likelihood of developing a chronic form.[14] 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:[54]




joint involvement, designating the metacarpophalangeal
joints, proximal interphalangeal joints, the interphalangeal
joint of the thumb, second through fifth metatarsophalangeal
joint and wrist as small joints, and shoulders, elbows,hip
joints, knees, and 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 rheumatoid factor as well
as 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, ESR, or elevated 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 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.[56] 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:[citation needed]



two or more swollen joints
morning stiffness lasting more than one hour for at least six
weeks
the detection of rheumatoid
factors or autoantibodies against ACPA such as autoantibodies
to mutated citrullinated vimentin can confirm the suspicion of
RA. A negative autoantibody result does not exclude a
diagnosis of RA.
Differential diagnoses[edit]
Several other medical conditions can resemble RA, and usually
need to be distinguished from it at the time of diagnosis:[57][58]








Crystal induced arthritis (gout, and 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 persons), 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 doublestranded 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
Reactive arthritis (previously Reiter's disease) – asymmetrically
involves heel, sacroiliac joints, and large joints of the leg. It is
usually associated withurethritis, conjunctivitis, iritis, painless
buccal ulcers, and keratoderma blennorrhagica.
Ankylosing spondylitis – this involves the spine, although a RAlike 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:[57]




Sarcoidosis, amyloidosis, and 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
by Streptococcus) is usually asymmetric, while RA usually
involves both sides of the body symmetrically.
Gonococcal arthritis (another bacterial arthritis) is also initially
migratory and can involve tendons around the wrists and
ankles.
Monitoring progression[edit]
There are many tools available for monitoring remission in
rheumatoid arthritis. Disease Activity Score of 28 joints (DAS28) is
widely used as an indicator of RA disease activity and response to
treatment, but is not always a reliable indicator of treatment
effect.[59] The joints included in DAS28 are (bilaterally): proximal
interphalangeal joints (10 joints), metacarpophalangeal
joints (10), wrists (2), elbows (2), shoulders (2) and knees (2). When
looking at these joints, both the number of joints with tenderness
upon touching (TEN28) and swelling (SW28) are counted. In
addition, the erythrocyte sedimentation rate (ESR) is measured.
Also, the affected person makes a subjective assessment (SA) of
disease activity during the preceding 7 days on a scale between 0
and 100, where 0 is "no activity" and 100 is "highest activity
possible". With these parameters, DAS28 is calculated
as:[60]
One major limitation of use of the DAS28 score in clinical setting is
low-grade synovitis may be missed
From this, the disease activity of the affected person can be
classified as follows:[60]
DAS28 decrease from initial value
Current
DAS28
> 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
Other tools to monitor remission in rheumatoid arthritis are: ACREULAR Provisional Definition of Remission of Rheumatoid arthritis,
Simplified Disease Activity Index (SDAI) and Clinical Disease
Activity Index (CDAI).[61]
Prevention[edit]
There is no known prevention for the condition other than the
reduction of risk factors.[62]
Management[edit]
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.[63]
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.[64] This can
often be achieved using two main classes of medications:
analgesics such as NSAIDs, and disease-modifying antirheumatic
drugs (DMARDs).[65] RA should generally be treated with at least
one specific anti-rheumatic medication.[63] 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.[66] Analgesics, other than NSAIDs, offer lesser, but some
benefit with respect to pain whilst not causing the same level of
gastrointestinal irritation.[3]
Lifestyle[edit]
Regular exercise is recommended as both safe and useful to
maintain muscles strength and overall physical function.[67] It is
uncertain if specific dietary measures have an effect.[68] Physical
activity is beneficial for persons with Rheumatoid arthritis
complaining of fatigue.[69] Occupational therapy has a positive role to
play in improving functional ability of persons with rheumatoid
arthritis.[70]
Disease modifying agents[edit]
Disease-modifying antirheumatic drugs (DMARDs) are the primary
treatment for RA.[3] 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.[3] DMARDs should be started early in the disease as they
result in disease remission in approximately half of people and
improved outcomes overall.[71] The following drugs are considered
as
DMARDs:methotrexate, hydroxychloroquine, sulfasalazine, leflunom
ide, TNF-alpha inhibitors, 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) andcyclosporin are less
commonly used due to more common adverse effects. Agents may
be used in combinations.[3] Methotrexate is the most important and
useful DMARD and is usually the first treatment.[64][65][72] Adverse
effects should be monitored regularly with toxicity including
gastrointestinal, hematologic, pulmonary, and hepatic.[72] Side
effects such as nausea, vomiting or abdominal pain can be reduced
by taking folic acid.[73] The most common undesirable effect is that it
increases liver enzymes in almost 15% of people.[72] 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.[74]
Biological agents should generally only be used if methotrexate and
other conventional agents are not effective after a trial of three
months.[75] They are associated with a higher rate of serious
infections as compared to other DMARDs.[76] These agents used to
treat rheumatoid arthritis include: tumor necrosis factor
alpha (TNFα) blockers[3] such as infliximab; interleukin 1 blockers
such as anakinra, monoclonal antibodies against B cells such
as rituximab and tocilizumab,[77] T cell costimulation blocker such as
abatacept among others. They are often used in combination with
either methotrexate or leflunomide.[3] In those who are well
controlled on TNF blockers decreasing the dose does not appear to
affect overall function.[78] Persons should be screened for latent
tuberculosis before starting any TNF blockers therapy to avoid
reactivation.[14]
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.[79] Abatacept appears effective for RA with 20% more people
improving with treatment than without but long term safety studies
are yet unavailable.[80] However, there is a lack of evidence to
distinguish between the biologics available for RA.[81] Issues with the
biologics include their high cost and association with infections
including tuberculosis.[3]
Anti-inflammatory agents[edit]
NSAIDs reduce both pain and stiffness in those with RA.[3] Generally
they appear to have no effect on people's long term disease course
and thus are no longer first line agents.[3][82] NSAIDs should be used
with caution in those with gastrointestinal, cardiovascular, or kidney
problems.[83][84][85] Use of methotrexate together with NSAIDS is safe,
if adequate monitoring is done.[86]
COX-2 inhibitors, such as celecoxib, and NSAIDs are equally
effective.[87] They have a similar gastrointestinal risk as an NSAIDs
plus a proton pump inhibitor.[88] In the elderly there is less
gastrointestinal intolerance to celecoxib than to NSAIDs
alone.[89] There however is an increased risk of myocardial
infarction with COX-2 inhibitors.[87] Anti-ulcer medications are not
recommended routinely but only in those high risk of gastrointestinal
problems.[90]
Glucocorticoids can be used in the short term for flare-ups, while
waiting for slow-onset drugs to take effect.[3] Injection of
glucocorticoids into individual joints is also effective.[3] While longterm use reduces joint damage it also results in osteoporosis and
susceptibility to infections, and thus is not recommended.[3]
Surgery[edit]
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.[3] Postoperatively,physiotherapy is always necessary.
Alternative medicine[edit]
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.[6] 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.".[91] Studies showing beneficial effects in RA on a wide variety of
CAM modalities are often affected by publication biasand are
generally not high quality evidence such as randomized controlled
trials (RCTs).[5]
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.[92]
There is some evidence that Tai Chi improves the range of motion
of a joint in persons with rheumatoid arthritis.[93] The evidence for
acupuncture is inconclusive[94] with it appearing to be equivalent to
sham acupuncture.[95]
Dietary supplements[edit]
The American College of Rheumatology states that no herbal
medicines have health claims supported by high quality evidence
and thus they do not recommend their use.[96] There is no scientific
basis to suggest that herbal supplements advertised as "natural" are
safer for use than conventional medications as both are chemicals.
Herbal medications, although labelled "natural", may be toxic or
fatal if consumed.[96] Some evidence supports omega-3 fatty acids
andgamma-linolenic acid in RA.[97] The benefit from omega-3
appears modest but consistent,[98] though the current evidence is not
strong enough to determine that supplementation with omega-3
polyunsaturated fatty acids (found in fish oil) is an effective
treatment for RA.[99] Gamma-linolenic acid, which may reduce pain,
tender joint count and stiffness, is generally safe.[100]
The following are under investigation for treatments for RA, based
on preliminary promising results (not recommended for clinical use
yet) : boswellic acid,[101]curcumin,[102] Devil's claw,[103][104] Euonymus
alatus,[105] and Thunder god vine (Tripterygium wilfordii).[106] NCCIH
has noted that, "In particular, the herb thunder god vine
(Tripterygium wilfordii) can have serious side effects."[6]
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.[5]
There is conflicting evidence on the role of Erythropoiesisstimulating agents for treatment of anemia in persons with
rheumatoid arthritis.[107]
Pregnancy[edit]
More than 75% of people with rheumatoid arthritis have symptoms
improve during pregnancy but might have worsenings after
delivery.[14] Methotrexate andleflunomide 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.[64][72] Low dose
of prednisolone, hydroxychloroquine and sulfasalazine are
considered safe in pregnant persons with rheumatoid arthritis.
Vaccinations[edit]
People with RA have an increased risk of infections and mortality
and recommended vaccinations can reduce these risks.[108] The
killed influenza vaccineshould be received
annually.[109] The pneumococcal vaccine should be administered
twice for people under the age 65 and once for those over
65.[110] 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 alphablocker.[111]
Prognosis[edit]
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.[citation needed]
Prognostic factors[edit]
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])
Increased clinical severity.
Mortality[edit]
RA reduces lifespan on average from three to twelve
years.[112] 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,[113] independent of other risk
factors such as diabetes, alcohol abuse, and elevatedcholesterol,
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.[114] 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.[115] 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
increase in total cholesterol and HDLc levels and no improvement
of the atherogenic index.[116]
Epidemiology[edit]
Disability-adjusted life year for RA per 100,000 inhabitants in 2004.[117]
no data
<40
40–50
50–60
90–100
100–110
110–120
120–130
60–70
70–80
80–90
130–140
>140
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.[3] In 2010 it resulted in about 49,000 deaths
globally.[118]
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.[14]
The age at which the disease most commonly starts is in women
between 40 and 50 years of age, and for men somewhat
later.[119] 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.
History[edit]
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.[citation needed] It was noted in skeletal remains of Native Americans
found in Tennessee.[120] In Europe, the disease is vanishingly rare
before the 17th century.[121] 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.[8] The name "rheumatoid
arthritis" itself was coined in 1859 by British rheumatologist
Dr Alfred Baring Garrod.[122]
An anomaly has been noticed from 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.[123]
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.[124][125] RA appears to some to have been
depicted in 16th-century paintings.[126] 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.
Historic treatments for RA have also included: rest, ice,
compression and elevation, apple diet, nutmeg, some light exercise
every now and then, nettles, beevenom, copper bracelets, rhubarb
diet, extractions of teeth, fasting, honey, vitamins, insulin, magnets,
and electroconvulsive therapy (ECT).[127] The Prosorba column blood
filtering device (removing IgG) was approved by the FDA in 1999 for
treatment of RA[128] However it was discontinued at the end of
2006.[129]
Etymology[edit]
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 or swollen or that the disease
may be made worse by wet weather.[9]