Rheumatoid arthritis (
RA) is a
chronic,
systemic inflammatory disorder that may affect many
tissues and organs, but principally attacks the joints producing an
inflammatory
synovitis that often
progresses to destruction of the articular cartilage and
ankylosis of the joints. Rheumatoid arthritis can
also produce diffuse inflammation in the
lungs,
pericardium,
pleura, and
sclera, and also
nodular lesions, most common in subcutaneous tissue under the
skin. Although the cause of rheumatoid
arthritis is unknown,
autoimmunity
plays a pivotal role in its chronicity and progression.
About 1% of the world's population is afflicted by 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. It can be a disabling and
painful
condition, which can lead to substantial loss of functioning and
mobility. It is diagnosed chiefly on symptoms and signs, but also
with
blood tests (especially a test
called
rheumatoid factor) and
X-rays. Diagnosis and long-term
management are typically performed by a
rheumatologist, an expert in the diseases of
joints and connective tissues.
Various treatments are available. Non-pharmacological treatment
includes
physical therapy,orthoses
and
occupational therapy.
Analgesia (painkillers) and
anti-inflammatory drugs, including
steroids, are used to suppress the
symptoms, while
disease-modifying
antirheumatic drugs (DMARDs) are often required to inhibit or
halt the underlying immune process and prevent long-term damage. In
recent times, the newer group of
biologics
has increased treatment options.
The name is based on the term "
rheumatic
fever", an illness which includes joint pain and is derived
from the Greek word
rheumatos ("flowing"). 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.
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. 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.
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.
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 may last 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 absent, and movements
induce pain due to the wear-and-tear. In RA, the joints are often
affected in a fairly symmetrical fashion, although this is not
specific, and the initial presentation may be asymmetrical.
Hands affected by RA
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
ulnar
deviation,
boutonniere
deformity,
swan neck
deformity and "Z-thumb," but these are of no more significance
to diagnosis or disability than other variants.
Skin
The
rheumatoid nodule,
which is often subcutaneous, is the feature most characteristic of
rheumatoid arthritis. 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
olecranon, the
calcaneal tuberosity, 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.
Several forms of
vasculitis
occur in rheumatoid arthritis. 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 due to the presence of an obliterative cutaneous
capillaropathy.
Other, rather rare, skin associated symtoms include:
Lungs
Fibrosis of the
lungs
is a recognised response to rheumatoid disease. It is also a rare
but well recognised 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.
Kidneys
Renal
amyloidosis can occur as a
consequence of chronic inflammation. Rheumatoid arthritis may
affect the kidney glomerulus directly through a vasculopathy or a
mesangial infiltrate but this is less well documented. Treatment
with
Penicillamine and
gold salts are recognized causes of
membranous nephropathy.
Heart and blood vessels
People with rheumatoid arthritis 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.
Other
- Ocular: 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 due to lymphocyte infiltration of
lachrymal 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 duct occlusion is
important.
- Hepatic: Cytokine production in joints and/or hepatic Kupffer cells leads to increased activity of
hepatocytes with increased production of acute-phase proteins, such
as C-reactive protein, and increased release of enzymes such as
alkaline phosphatase into the blood. In Felty's syndrome, Kuppfer 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. Because Kuppfer cells are not within the liver
parenchyma, there is little or no evidence of hepatitis. Hepatic
involvement in RA is essentially asymptomatic.
- Hematological: Anemia is by far the most
common abnormality of the blood cells. The red cells are of normal
size and colour (normocytic). A low white blood cell count
(neutropenia) or 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: Peripheral
neuropathy and mononeuritis
multiplex may occur. The most common problem is carpal tunnel
syndrome due to 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 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 lymphoma is
increased in RA, although it is still uncommon.
Diagnosis
Imaging
X-ray of the hand in rheumatoid
arthritis.
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 sublaxation. 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
and ultrasound are also used in rheumatoid arthritis.
Blood tests
When RA is clinically suspected,
immunological studies are required, such as
testing for the presence of
rheumatoid
factor (RF, a specific
antibody). A
negative RF does not rule out RA; rather, the arthritis is called
seronegative. This is the case
in about 15% of patients. 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, and in
approximately 10% of the healthy population, therefore the test is
not very specific.
Because of this low
specificity,
new serological test have been developed, which tests for the
presence of so called anti-citrullinated protein antibodies
(
ACPAs). 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%. As with RF, there is evidence for ACPAs
being present in many cases even before onset of clinical
disease.
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
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
rheumatoid arthritis 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,
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, a seronegative,
usually juvenile, variant of rheumatoid.
Diagnostic criteria
The
American College of
Rheumatology has defined (1987) the following criteria for the
classification of rheumatoid arthritis:
- Morning stiffness of >1 hour most mornings for at least 6
weeks.
- Arthritis and soft-tissue swelling of >3 of 14
joints/joint groups, present for at
least 6 weeks
- Arthritis of hand joints, present for at least 6 weeks
- Symmetric arthritis, present for at least 6 weeks
- Subcutaneous nodules in specific places
- Rheumatoid factor at a level
above the 95th percentile
- Radiological changes suggestive of joint erosion
At least four criteria have to be met for classification as RA.
These criteria are not intended for the diagnosis for routine
clinical care; they were primarily intended to categorize research.
For example: one of the criteria is the presence of bone erosion on
X-Ray. Prevention of bone erosion is one of the main aims of
treatment because it is generally irreversible. To wait until all
of the ACR criteria for rheumatoid arthritis are met may sometimes
result in a worse outcome. Most sufferers and rheumatologists would
agree that it would be better to treat the condition as early as
possible and prevent bone erosion from occurring, even if this
means treating people who don't fulfill the ACR criteria. The ACR
criteria are, however, very useful for categorising established
rheumatoid arthritis, for example for epidemiological
purposes.
Differential diagnosis
Several other medical conditions can resemble RA, and usually need
to be distinguished from it at the time of diagnosis:
- Crystal induced arthritis (gout, and
pseudogout) - usually involves particular
joints and can be distinguished with aspiration of joint fluid if
in doubt
- Osteoarthritis - distinguished
with X-rays of the affected joints and blood
tests
- 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
- Reactive arthritis
(previously Reiter's disease) - asymmetrically involves heel,
sacroiliac joints, and large joints of
the leg. It is usually associated with urethritis, conjunctivitis, iritis,
painless buccal ulcers, and keratoderma blennorrhagica.
- Ankylosing spondylitis -
this involves the spine and is usually diagnosed in males, although
a RA-like symmetrical small-joint polyarthritis may occur in the
context of this condition.
Rarer causes that usually behave differently but may cause joint
pains:
- 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 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.
Pathophysiology
Joint abnormalities in rheumatoid
arthritis
Rheumatoid arthritis is a form of
autoimmunity, the causes of which are still
incompletely known. It is a systemic (whole body) disorder
principally affecting synovial tissues.
The key pieces of evidence relating to pathogenesis are:
1. A genetic link with
HLA-DR4 and related
allotypes of
MHC Class II and the T
cell-associated protein
PTPN22.
2. A link with cigarette smoking that appears to be causal.
3. A dramatic response in many cases to blockade of the cytokine
TNF (alpha).
4. A similar dramatic response in many cases to depletion of
B lymphocytes, but no comparable
response 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
rheumatoid factors (RF), and
antibodies to citrullinated
peptide (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
citrullination but the stochastic (random)
epidemiology suggests that the rate limiting step in genesis of
disease in predisposed individuals may be an inherent stochastic
process within the immune response such as immunoglobulin or T cell
receptor gene recombination and mutation. (See entry under
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
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.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 favour immune
complexes (based on antibody synthesised elsewhere) as the
initiators, even if not the sole perpetuators of inflammation.
Moreover, work by Thurlings and others in Paul-Peter Tak's group
and also by Arthur Kavanagh's group suggest that if any immune
cells are relevant locally they are the plasma cells, which derive
from B cells and produce in bulk the antibodies selected at the B
cell stage.
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 patients 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 due to
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.
Possible infectious trigger
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
molecular mimicry. Some infectious
organisms suspected of triggering rheumatoid arthritis include
Mycoplasma,
Erysipelothrix,
parvovirus B19 and
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
herpesvirus
infections:
Epstein-Barr virus
(EBV) and
Human Herpes Virus 6
(HHV-6).Individuals with RA are more likely to exhibit an abnormal
immune response to the Epstein-Barr virus.
The allele HLA-DRB1*0404 is associated with low frequencies of
T cells specific for the EBV
glycoprotein 110 and predisposes one to develop
RA.
There is no clear evidence that physical and emotional effects,
stress and improper diet 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, as suggested by Edwards et al..
Continued 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
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 rheumatoid arthritis, namely cigarette smokingOther
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 child-birth, 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).
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.
Treatment
There is no known cure for rheumatoid arthritis, but many different
types of treatment can alleviate symptoms and/or modify the disease
process.
The goal of treatment is two-fold: alleviating the current
symptoms, and preventing the future destruction of the joints with
the resulting handicap if the disease is left unchecked. These two
goals may not always coincide: while pain relievers may achieve the
first goal, they do not have any impact on the long-term
consequences. For these reasons, most authorities believe that most
RA should be treated by at least one specific anti-rheumatic
medication, also named DMARD (see below), to which other
medications and non-medical interventions can be added as
needed.
Cortisone therapy has offered relief in
the past, but its long-term effects have been deemed undesirable..
However, cortisone injections can be valuable adjuncts to a
long-term treatment plan, and using low dosages of daily cortisone
(e.g., prednisone or prednisolone, 5-7.5 mg daily) can also
have an important benefit if added to a proper specific
anti-rheumatic treatment.
Pharmacological treatment of RA can be
divided into disease-modifying antirheumatic drugs (DMARDs),
anti-inflammatory agents and
analgesics.Treatment also includes rest and
physical activity.
Disease modifying anti-rheumatic drugs (DMARDs)
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 ray 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.
Traditional small molecular mass drugs
Chemically synthesised
DMARDs:
Cytotoxic drugs:
The most important and most common adverse events relate to
liver and
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.
Methotrexate is considered by many rheumatologists to be the most
important and useful DMARD, largely because of lower drop-out rates
for reasons of toxicity. Nevertheless, methotrexate is often
considered as a very 'toxic' drug. This reputation is not entirely
justified, and at times can result in people being denied the most
effective treatment for their arthritis. Although methotrexate does
have the potential to suppress bone marrow or cause hepatitis,
these effects can be monitored using regular blood tests, and the
drug withdrawn at an early stage if the tests are abnormal before
any serious harm is done (typically the blood tests return to
normal after stopping the drug). 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). 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.
Biological agents
Biological agents (biologics) are produced through genetic
engineering, and include :
Numerous biologics are in clinical trials (eg. Ocrelizumab, Ofatumumab, Golimumab, Certolizumab pegol).
Anti-inflammatory agents and analgesics
Anti-inflammatory agents include:
Analgesics include:
Historic treatments for RA have also included:
rest, ice , compression and elevation,
acupuncture,
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)..
Most of these have either had no effect at all, or their effects
have been modest and transient, while not being
generalizable.
Other therapies
Other therapies are
weight loss,
orthoses, occupational therapy,
podiatry,
physiotherapy,
immunoadsorption therapy,
joint injections, and special tools to
improve hard movements (e.g. special tin-openers). Regular exercise
is important for maintaining joint mobility and making the joint
muscles stronger.
Ayurveda, mostly in southern India, is
another source of treatment, and while it is popular in India there
are no studies to show that it benefits patients with RA.
Radon therapy, popular in Germany and Eastern
Europe, can induce beneficial long-term effects for rheumatoid
arthritis.
A survey in the United Kingdom between 1998 and 2002 found
arthritis to be reported among the five most common reasons for the
medicinal use of cannabis.
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.
The effectiveness of treating RA with
acupuncture
is inconclusive, and "more rigorous research seems to be warranted"
according to one study.
Severely affected joints may require
joint replacement surgery, such as knee
replacement.
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.
Disability
- Daily living activities are impaired in most individuals.
- After 5 years of disease, approximately 33% of sufferers will
not be working.
- After 10 years, approximately half will have substantial
functional disability.
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.
Mortality
Estimates of the life-shortening effect of RA vary; most sources
cite a lifespan reduction of 5 to 10 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.
Epidemiology
[[Image:Rheumatoid arthritis world map - DALY -
WHO2004.svg|thumb|
Disability-adjusted life year
for rheumatoid arthritis per 100,000 inhabitants in 2004.
]]The
incidence of RA is in
the region of 3 cases per 10,000 population per annum. Onset is
uncommon under the age of 15 and from then on the incidence rises
with age until the age of 80. The
prevalence rate is 1%, with women affected three
to five times as often as men. It is 4 times more common in smokers
than non-smokers.
Some Native American groups
have higher prevalence rates (5-6%) and people from the Caribbean
region have lower prevalence rates.
First-degree relatives prevalence rate is 2-3% and disease
genetic concordance in
monozygotic twins is approximately
15-20%.
It is strongly associated with the inherited tissue type
Major histocompatibility
complex (MHC) antigen
HLA-DR4 (most specifically DR0401
and 0404) — hence family history is an important risk factor.
Rheumatoid arthritis affects women three times more often than men,
and it can first develop at any age. 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. 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
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 rheumatoid arthritis.
It was noted in skeletal remains of Native
Americans found in Tennessee
. In the Old World the disease is vanishingly
rare before the 1600s. and on this basis investigators believe it
spread across the Atlantic during the
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. Jim Mobley, at Pfizer, has discovered a historical
pattern of epidemics of tuberculosis followed by a surge in the
number of rheumatoid arthritis cases a few generations later.
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
Peter Paul Rubens may
possibly depict the effects of rheumatoid arthritis. In his later
paintings, his rendered hands show, in the opinion of some
physicians, increasing deformity consistent with the symptoms of
the disease. Rheumatoid arthritis appears to some to have been
depicted in 16th century paintings. However, it is generally
recognised in art historical circles that the painting of hands in
the sixteenth and seventeenth 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 Salpêtrière
Hospital
in Paris. The name "rheumatoid arthritis"
itself was coined in 1859 by British rheumatologist Dr
Alfred Baring Garrod.
Notable cases
- Dorothy Hodgkin, Nobel prize
winning scientist, developed severe deforming rheumatoid arthritis
at age 28. In spite of this she continued her career and developed
X-ray crystallography,
underpinning a lot of information about rheumatoid arthritis,
discovered the structure of insulin and
enabled discovery of the genetic
code.
- Auguste Renoir, impressionist
painter, whose later 'softer' style might have reflected in some
way his severe disability.
- 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.
- James Coburn claimed to have healed
the condition using pills containing a sulfur-containing compound
on his return to acting.
- 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.
- Bob Mortimer British comedian and
actor.
- Kathleen Turner and Aida Turturro have worked to raise public
awareness of the condition
- Billy Bowden, international cricket
umpire who had to retire from active playing due to RA
- Melvin Franklin, bass singer of
the Temptations. He treated RA with cortisone shots so he could
perform.
- Jamie Farr, American actor, famous
for his role as Max Klinger on the
1970s television series M*A*S*H.
- Gabi Rojas, An American dancer, She
appeared on So You Think You
Can Dance Season 5 making the top 54 in Vegas.
- Sandy Koufax, An American
Hall-of-Fame baseball pitcher who played from 1955 to 1966 for the
Los Angeles Dodgers.
See also
References
- Jijith Krishnan,Document on Rhuematoid
arthritis
-
http://www.fda.gov/Drugs/ResourcesForYou/HealthProfessionals/ucm107046.htm
- http://www.arthritis.org/drugs-in-pipeline-ra-focus.php "New RA
Drugs in the Pipeline"
- Fresenius HemoCare, Inc., "New Hope for Rheumatoid Arthritis
Patients," press release, September 17, 1999.
- http://arthritis.about.com/od/arthqa/f/prosorba.htm
- Excess mortality in rheumatoid arthritis
- The second largest contributor of mortality is
cerebrovascular disease. Increased risk of heart disease in
rheumatoid arthritis patients
- Cardiac disease in rheumatoid arthritis
- http://mcclungmuseum.utk.edu/research/renotes/rn-05txt.htm
Tennessee Origins of Rheumatoid Arthritis
- http://www.arc.org.uk/newsviews/arctdy/104/bones.htm Bones of
Contention
- Scientist finds surprising links between arthritis
and tuberculosis
- http://japan.medscape.com/viewarticle/538251 Did RA travel from
New World to Old? The Rubens connection
- reproduced in
-
http://www.bbc.co.uk/pressoffice/bbcworldwide/worldwidestories/pressreleases/2002/02_february/radiotimes_bob_mortimer.shtml
External links
- Patient-led charity for people with Rheumatoid Arthritis
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