PROGRAM PEMULIHAN PERUBATAN CARAKERJA
KOLEJ SAINS KESIHATAN BERSEKUTU
KEMENTERIAN KESIHATAN MALAYSIA
SUNGAI BULOH, SELANGOR
RHEUMATOID ARTHRITIS
1. STEPHENNUS STANLEY CHIAM
2. AZMI RAMAN BIN DOUSIN
3. ALVIN DULAMIT
Pengajar: En. Rohaizat bin Ramli
Causes of Rheumatoid Arthritis
Clues from History and Geography
A study of the history and geography of RA provides some intriguing clues with regards to the
cause of the disease. Within Europe there are no definite descriptions of RA before 1800. It is
surprising that the typical hand deformities which often develop after many years of disease
particularly if it is untreated, do not appear in medical or ordinary literature, paintings, or skeletal
remains. This suggests that RA may be a "modern disease". By contrast, in North America,
skeletons have been found dating back several thousand years which do show evidence of RA.
To this day the highest frequency of RA is found amongst Native American peoples. This
suggests that RA may have originated in the New World and been transported to the Old World.
The first candidate that springs to mind is an infection. However, we must not forget that other
items such as tobacco and the potato were also transported from the New World to the Old.
The occurrence of RA is not the same throughout the world. RA is rare in less developed and
rural parts of the world. One large study in Nigeria failed to find a single case. RA is also rare in
rural China and Indonesia. An intriguing pair of studies from South Africa found a low frequency
of RA amongst members of an African tribal group in a rural area and similar rates to those
found in Europeans amongst members of the same tribal group who had moved to live in the
city. This led to a theory that RA might be related to an industrialised lifestyle. However the
same pattern was not found amongst the Chinese. Low frequencies of RA were found in Hong
Kong which is a highly industrialised society. Perhaps the African people changed their diet
when they moved to the city whereas the Chinese people did not.
1
Genetics
Genetic factors account for 50% of the risk for developing RA. Approximately 60% of US
patients with rheumatoid arthritis carry a shared epitope of the HLA-DR4 cluster, which
constitutes one of the peptide-binding sites of certain HLA-DR molecules associated with RA
(eg, HLA-DR beta *0401, 0404, or 0405); in addition, HLA-DR1 (HLA-DR beta *0101) also
carries this shared epitope and confers risk, particularly in certain southern European areas.
Other HLA-DR4 molecules (eg, HLA-DR beta *0402) do not share the same epitope and do not
confer risk.
Genes other than those of the major histocompatibility complex (MHC) are also involved, and
results from sequencing genes of families with RA suggest the presence of several susceptibility
genes and several resistance genes. Juvenile idiopathic arthritis is a genetically complex trait in
which multiple genes are important for disease onset and manifestations.
The IL2RA/CD25 gene has recently been implicated as a juvenile idiopathic arthritis
susceptibility locus, as has the VTCN1 gene.
Infectious agents
For many decades, numerous infectious agents have been suggested to induce RA. Among
these are Mycoplasma organisms, Epstein-Barr and rubella viruses, and others. This
supposition is further supported indirectly by the following:

Occasional reports of flulike disorders preceding the start of arthritis

The inducibility of arthritis in experimental animals with different bacteria or bacterial products
(eg, streptococcal cell walls)

The presence of bacterial products, including bacterial RNA, in patients' joints

The activity of several agents that have antimicrobial effects as disease-modifying drugs (eg,
gold salts, antimalarials, minocycline)
Hormones
Sex hormones may play a role in RA, as evidenced by the disproportionate number of females
with this disease, its amelioration during pregnancy, its recurrence in the early postpartum
period, and its reduced incidence in women using oral contraceptives. Hyperprolactinemia may
be a risk factor for RA
2
Immunologic factors
All of the major immunologic elements play fundamental roles in the initiation, propagation, and
maintenance of the autoimmune process of RA. The exact orchestration of the cellular and
cytokine events that lead to pathologic consequences, such as synovial proliferation and
subsequent joint destruction, is complex. It involves T and B lymphocytes, antigen-presenting
cells (APCs) (eg, B cells, macrophages, dendritic cells), and numerous cytokines. Aberrant
production and regulation of both proinflammatory and anti-inflammatory cytokines and cytokine
pathways are found in RA.
T cells are assumed to play a pivotal role in the initiation of RA, and the key player in this
respect is assumed to be the T helper 1 (Th1) CD4 cells. (Th1 cells produce IL-2 and interferon
[IFN] gamma.) These cells may subsequently activate macrophages and other cell populations,
including synovial fibroblasts. Macrophages and synovial fibroblasts are the main producers of
the proinflammatory cytokines TNF-alpha and IL-1. Experimental models suggest that synovial
macrophages and fibroblasts may become autonomous and thus lose responsiveness to T-cell
activities in the course of the disease.
B cells are important in the pathologic process and may serve as antigen-presenting cells. B
cells also produce numerous autoantibodies (eg, RF,to citrullinated proteins) and secrete
cytokines.
The hyperactive and hyperplastic synovial membrane is ultimately transformed into pannus
tissue and invades cartilage and bone, the latter being degraded by activated osteoclasts. The
major difference between RA and other forms of inflammatory arthritis, such as psoriatic
arthritis, does not lie in their cytokine patterns but rather in the highly destructive potential of the
RA synovial membrane and in the local and systemic autoimmunity. Whether these 2 events are
linked is unclear; however, the autoimmune response conceivably leads to the formation of
immune complexes that activate the inflammatory process to a much higher degree than
normal. This theory is supported by the much worse prognosis of RA among patients with
positive RF results.
3
Risk Factor of Rheumatoid Arthritis
1. Hormonal factors
Throughout the world, RA is more common in women than in men. This suggests that hormonal
factors may play a part in the development of the disease. RA usually goes into remission
during pregnancy. It is also very unusual for the disease to begin during pregnancy. However, in
the few weeks after delivery, women with RA often experience a relapse and there is a much
higher frequency of development of RA. This may be because prolactin, the hormone which is
responsible for milk production, enhances inflammation.
The oral contraceptive pill has probably played a major part in reducing the occurrence of RA in
younger women in the developed world over the last thirty to forty years. The incidence of RA in
women who have ever taken the Pill is around half that in women who have never taken the Pill.
It is not clear whether this protection will be lifelong. It is possible that the onset of RA has
simply been delayed until after the menopause. There is as yet no evidence that hormone
replacement therapy has any effect on the development of RA nor that the pill has any effect on
the course of RA in women who have already developed the disease.
2. Other Medical Conditions
There has always been a widely held belief that RA ought to be caused by an infection. Many
researchers have dedicated their lives to trying to identify that agent, without success. It seems
clear now that no single germ causes all cases of RA. However, in a substantial proportion of
cases RA begins within a few weeks of an infection of some sort. It is not that the infection
persists but that the immune response to the infection does not "switch off" as it should. Arthritis
is part of that immune response.
Immunisation (which mimics, in a controlled way, the development of infection) can act as a
trigger for RA in some people. It is likely that these people would have developed RA if they had
caught the natural infection from which the immunisation was protecting them.
RA is more common in people who already have another auto-immune disease, probably
because of the shared genetic background.
4
3. Personal Risk Factors for the Development of RA
The risk of developing RA is substantially higher in smokers. There is also some evidence that
smoking influences the course of RA. Smoking appears to have beneficial effects on the amount
of pain and joint tenderness which people with RA experience and this may be why people with
RA find it difficult to stop smoking. However, people with RA who continue to smoke are more
likely to develop what is called extra-articular disease (nodules, involvement of the lung or
inflammation of the blood vessels). People with RA also have a higher death rate from lung
cancer than the general population and this is probably explained by the higher proportion of
smokers amongst people with RA.
By contrast there is no evidence that alcohol consumption has any influence on the
development of RA or its subsequent course.
There is some evidence that certain components of the diet may increase the risk of RA in
susceptible individuals. Diets high in red meat and low in vitamin C and other components of
brightly coloured fruit and vegetables appear to carry an enhanced risk of RA. Conversely, the
so-called Mediterranean diet appears to be relatively protective.
In people with many of the genetic risk factors for RA, exposure to a single environmental risk
factor may trigger RA. However, in the majority of people these factors (and others which have
not yet been identified) probably act cumulatively, slowly lowering the threshold for the
development of RA.
5
What increase your risk?
The only known risk factor for rheumatoid arthritis is a possible inherited factor in some families
(genetic predisposition). A genetic factor may affect how the immune systemworks. It can cause
inflammation and eventual destruction of the membranes that line the joints.
Other factors that may increase your risk for rheumatoid arthritis include:

Being female. Rheumatoid arthritis affects women 2 to 3 times as often as men.1

Being between the ages of 40 and 60. Rheumatoid arthritis can begin at any age, but it most
often begins in adulthood.2
Call your health professional immediately if you have:

Sudden, unexplained swelling and pain in any joint or joints.

Joint pain associated with a fever or rash.

Pain that is so severe that you cannot use the joint.
Call your health professional within the next few days if you have:

Mild to moderate joint pain that continues and has not improved for over 6 weeks.

Side effects that occur with large doses ofnonsteroidal anti-inflammatory drugs (NSAIDs) or
other medicine used to treat your arthritis.
Watchful Waiting
It is reasonable to try home treatment for mild joint pain and stiffness. If there is no improvement
after 6 weeks, or if any other symptoms are present, call your doctor.
Early treatment can slow and sometimes prevent significant joint damage. So if you have
symptoms similar to rheumatoid arthritis, see your doctor to find out if you have rheumatoid
arthritis. Early diagnosis and treatment allows for possible reduction of joint pain, slows joint
destruction, and reduces the chance of permanent disability.
6
Different characteristics between Osteoarthritis and Rheumatoid Arthritis?
Rheumatoid Arthritis and Osteoarthritis are different types of arthritis. Although they share some
similar characteristics, each has different symptoms and requires different treatment. Therefore,
an accurate diagnosis is important.
How Do Osteoarthritis and Rheumatoid Arthritis Differ?
Osteoarthritis (also referred to as degenerative joint disease or wear-and-tear arthritis) is
caused by the breakdown of joint cartilage. Cartilage acts as a cushion between the bones that
form a joint. Cartilage loss can cause bone to rub on bone in a joint -- a condition that
isvery painful. Usually osteoarthritis begins in a single joint.
Rheumatoid arthritis is a chronic, inflammatory type of arthritis. It is also classified as an
autoimmune disease (i.e., immune cells attack the body's own healthy tissues).
The synovium (lining of the joint) is primarily affected by rheumatoid arthritis, but organs bodywide can be affected as well. Multiple joints are usually involved with rheumatoid arthritis.

Rheumatoid Arthritis - Explained With Pictures
What Causes Osteoarthritis and Rheumatoid Arthritis?
Osteoarthritis is mostly a consequence of aging. Water content of cartilage increases while
protein composition of cartilage degenerates. Other factors that may increase the risk of
developing osteoarthritis include:

joint injury

repetitive use or stress of joints

being overweight

family history/genetics
With regard to rheumatoid arthritis, researchers have worked for years to find the cause of the
abnormal autoimmune response associated with the disease. No single cause has been found.
Common theories point to a genetic predisposition and a triggering event.
7
What Symptoms Point to Osteoarthritis or Rheumatoid Arthritis?
Osteoarthritis primarily affects the joints. The most common symptom associated with
osteoarthritis is pain in the affected joint after repetitive use or activity. Morning stiffness lasts a
half hour or less. Joint pain is often worse later in the day. The affected joint can also swell, feel
warm, and become stiff after prolonged inactivity. Bone spurs, bony enlargements (Heberden's
nodes and Bouchard's nodes), and limited range of motion are also characteristics of
osteoarthritis.
Rheumatoid arthritis symptoms include:

joint pain

joint swelling or effusion

joint stiffness

redness and/or warmth near the joint

restricted range of motion
Morning stiffness lasting more than an hour, involvement of the small bones of the hands and
feet, extreme fatigue, rheumatoid nodules, and symmetrical joint involvement (both knees, not
just one) are all characteristics of rheumatoid arthritis. There also can be lung, kidney, or
cardiac involvement.

Rheumatoid Arthritis Screening Quiz
How is Osteoarthritis and Rheumatoid Arthritis Diagnosed?
This is where some similarities occur. X-rays of affected joints can show joint damage
associated with osteoarthritis or rheumatoid arthritis.Arthrocentesis, joint fluid removal, and joint
fluid analysis are possible procedures that can assess osteoarthritis or rheumatoid arthritis. The
results differentiate which type of arthritis is involved.
Blood tests cannot definitively diagnose osteoarthritis, but may be used to rule out other
conditions, including rheumatoid arthritis. Test results, a physical examination, and the patient's
medical history together can help determine a diagnosis.
8
Laboratory tests which are commonly ordered to help diagnose rheumatoid arthritis include:

rheumatoid factor

erythrocyte sedimentation rate

C-reactive protein

anti-CCP test
How is Osteoarthritis and Rheumatoid Arthritis Treated?
Treatment options for osteoarthritis focus on pain relief and restoring function to the affected
joint. Medications are commonly used to treat osteoarthritis. Nonsteroidal anti-inflammatory
drugs, analgesics, as well as steroid injections are used to treat pain and inflammation. Physical
therapy that focuses on exercises to strengthen and stabilize the joint,support/bracing, heat,
rest, and weight reduction are all important to a successful treatment regimen. Alternative
treatments are used, such as massage therapy, acupuncture, and more.
The primary treatment for rheumatoid arthritis is medication. There are 5 categories of
medication commonly used to treat rheumatoid arthritis:

Biologics (Enbrel, Remicade, Humira, Rituxan, Orencia)

DMARDs (disease-modifying anti-rheumatic drugs such as methotrexate)

Corticosteroids (such as prednisone, hydrocortisone)

NSAIDs (nonsteroidal anti-inflammatory drugs such as Celebrex and naproxen)

Analgesics (painkillers)
Along with medication, some forms of alternative/complementary treatment or local steroid
injections may help relieve pain for rheumatoid arthritis. For both rheumatoid arthritis and
osteoarthritis, the last-resort treatment option is surgery -- arthroscopy, arthrodesis (fusion), and
arthroplasty (joint replacement).
9
The Prevalence of Osteoarthritis and Rheumatoid Arthritis - How Do They Compare?
Osteoarthritis affects over 21 million people in the United States. Osteoarthritis occurs more
frequently in males before age 45 and more frequently in females after age 55. All races in the
United States appear to be affected equally by osteoarthritis. According to the American College
of Rheumatology, 70% of people over the age of 70 have x-ray evidence of osteoarthritis.
Approximately 2.1 million people in the United States have rheumatoid arthritis and about 1 to
2% of the world's population are affected by rheumatoid arthritis. About 75% of rheumatoid
arthritis patients are women. Men, women, and even children can develop rheumatoid arthritis,
though. Typically, disease onset for rheumatoid arthritis occurs between 30 and 60 years of
age.
10
Comparison chart
Associatedsymptoms:
Osteoarthritis
Rheumatoid Arthritis
Symptoms occur in isolation,
Frequent feelings of "being
with no
sick inside," with
systemic symptoms such as
fevers, weight loss, or
fatigue, fever, organ
involvement of other organ
involvement; can develop
systems - nodules may
Heberden's or Bouchard's
develop on sclera or lungs;
nodes
may develop Sjogren's or
Felty syndrome
Disease Process:
Normal wear and tear
Autoimmune
Gender:
Common in both men and
Affects more women than
women. Before 50 more men
men
than women, after 50 more
women than men
Severity:
Less severe
More severe
Treatment:
NSAIDs
NSAIDs,Steroids, DMARDs,
biological therapies
pain w/ movement:
movement increases pain
movement decreases pain
Diagnosis:
x-ray
American Rheumatism
Association Criteria
Pattern of joints that
Asymmetrical & may spread
Symmetrical - often affects
are affected:
to the other
small and large joints on
side. Symptoms begin
both sides of the body, such
gradually and are often
as both hands, both wrists
Osteoarthritis
Rheumatoid Arthritis
limited to one set of joints,
or elbows, or the balls of
usually the finger joints
both feet.
closest to the fingernails or
the thumbs, large weightbearing joints.
Age of onset:
Most commonly occurs in
Usual age of onset is 20-40
individuals over the age of
years.
50.
Cause:
wear and tear associated w/
Classified as
aging or injury, also caused
an autoimmune disease, No
by injuries to the joints,
real known cause.
obesity, heredity, overuse of
the joints from sports
speed of onset:
slow, over years
Relatively rapid, over weeks
to months
Joint symptoms:
Joints painful but without
Joints are painful, swollen,
swelling; affects joints
and stiff; affects joints
asymmetrically; affects
symmetrically; affects
bigger joints such as hips &
smaller joints such as hands
knees. Localized with
& ankles. Systemic with
variable, progressive course
exacerbations and
remissions
Clinical:
One or several joints;
Joints are swollen, red,
enlarged, cool, and hard on
warm, tender, and
palpation; limited ROM
painful;several joints
involved; limited ROM
Osteoarthritis
Rheumatoid Arthritis
Presence of
Systemic symptoms are not
Frequent fatigue and a
symptoms affecting
present.
general feeling of being ill
the whole body
are present
(systemic):
Duration of morning
Morning stiffness lasts less
Morning stiffness lasts
stiffness:
than 60 mins; tends to get
longer than 1 hour; worse in
worse later throughout day
AM; stiffness occurs in AM
& periods of rest
Effusions:
Uncommon
Common
Nodules:
Herberden's & Bouchard's
Present, especially on
nodes
extensor surfaces
13
1. Professor Deborah Symmons, MD. (2004, Jan 07). National Rheumatoid Arthritis Society
[WWW page]. Cited from:
http://www.nras.org.uk/about_rheumatoid_arthritis/what_is_ra/why_me/what_is_the_cause_of_r
heumatoid_arthritis_nongenetic_factors.aspx
2 – 3. Katherine Temprano, MD. (2012, Aug 20). Rheumatoid Arthritis [WWW page]. Cited from:
http://emedicine.medscape.com/article/331715-overview#aw2aab6b2b4
4 – 5. Professor Deborah Symmons, MD. (2004, Jan 07). National Rheumatoid Arthritis Society
[WWW page]. Cited from:
http://www.nras.org.uk/about_rheumatoid_arthritis/what_is_ra/why_me/what_is_the_cause_of_r
heumatoid_arthritis_nongenetic_factors.aspx
6. William C. Shiel Jr., MD, FACP, FACR., and Melissa Conrad Stöppler, MD, Chief Medical
Editor. Rheumatoid Arthritis : What Increases Your Risk of Rheumatoid Arthritis [WWW page],
Cited from: http://www.emedicinehealth.com/rheumatoid_arthritis-health/page5_em.htm
7 – 10. Carol Eustice, BS, MT(ASCP). Osteoarthritis and Rheumatoid Arthritis - What's the
Difference? : Understanding Two Common Types of Arthritis [WWW page] . Cited from:
http://osteoarthritis.about.com/od/osteoarthritis101/a/OA_RA.htm
11 – 13. Osteoarthritis vs Rheumatoid Arthritis. (n.d.). In Diffen.( 2012, Aug 20), Cited from :
http://www.diffen.com/difference/Osteoarthritis_vs_Rheumatoid_Arthritis