RHEUMATOID

ARTHRITIS

Prepared by:

 ASYA'ARI BIN ARIF

 RASHEEDI JUZAIMIE BIN JUSOH
 MUHAMMAD AFIQ BIN MOHD RAZALI
 NUR NADIATUL NABILA BT AHMAD SAIFUDDIN
 DEFINITION

• RA is a systemic , chronic
inflammation disease affecting many
tissues
• principally attacking the joints to
produce nonsuppurative proliferative
synovitis
• 3 to 5 times more common in women
than men
• peak incidence : 2nd to 4th decades of
life
 EPIDEMIOLOGY AND HISTORY

Gender
• Women are two-to-three times more likely than men to develop
rheumatoid arthritis. The exact cause for this is not known, but
it may be related to the hormone, oestrogen

Age
• Rheumatoid arthritis can develop at any age but it is more
common in older people. It is most likely to be diagnosed in
people between 40 and 60 years of age
• .
Family history
• Although rheumatoid arthritis is not a hereditary disease,
certain genes can make a person more susceptible to it. This
means that people with close relatives who suffer from
rheumatoid arthritis have a higher than usual risk of developing
it themselves because they may have inherited the same
genes. However, they are still more likely not to get the disease
than to get it.
• .
Family history
• Although rheumatoid arthritis is not a hereditary disease,
certain genes can make a person more susceptible to it.
This means that people with close relatives who suffer from
rheumatoid arthritis have a higher than usual risk of
developing it themselves because they may have inherited
the same genes. However, they are still more likely not to
get the disease than to get it.

Smoking
• People who smoke have a higher risk of developing
rheumatoid arthritis than those who do not.

Picture of people of different races

• In Europe and North America, rheumatoid arthritis affects
0.5–1% of the population in total. However, it is much more
common in Native Americans (affecting over 5%) and less
common in African and Asian people. This suggests that
there are genetic factors involved in the development of the
disease.
 CAUSES
• The cause of rheumatoid arthritis is unknown.
• Even though infectious agents such as
viruses, bacteria, and fungi have long been
suspected, none has been proven as the
cause
• It is believed that the tendency to develop
rheumatoid arthritis may be genetically
inherited
• Environmental factors also seem to play some
role in causing rheumatoid arthritis. For
example, scientists have reported that smoking
tobacco increases the risk of developing
rheumatoid arthritis.
MORPHOLOGY

A)Articular Lesion
 The most severe form
 Present as symmetric arthritis,affect small joint of
hand,feet,ankle,knees,wrists,elbows and
shoulders.
 Typical in proximal interphalangeal and
metacarpophalangeal
 Frequent in cervical spine
1. Joint
- synovium becomes grossly edematous, thickened and
hyperplastic(bulbous fronds)

-Histologic features:
i. Dense perivascular inflammatory cell infiltrate(form
lymphoid follicle) in synovium composed of CD4+ T Cell,
B cell,plasma cell,dendritic cells and macrophage.
ii. Increased vascularity due to angiogenesis and
vasodilation.
iii. Aggregation of organizing fibrin on synovial surface and
float in joint space as ‘rice bodies’
iv. Accumulation of neutrophils in synovial fluids and along
synovium surface.
v. Increased osteoclast activity in the underlying
bones,leading to synovial penetration and bone erosion.
vi. Pannus formation
Villous hypertrophy of the synovium is seen, forming large papillary projections
on the surface. These are characterized by proliferation of the synoviocytes and
aggregates of inflammatory cells within the villous stroma.
At higher magnification ,subsynovial
tissue containing a dense lymphoid
aggregate is seen
The region of the synovial lining that erodes into the bone, which is known as the pannus,
contains macrophages, fibroblasts and osteoclasts, which contribute to the cartilage and bone
destruction76. The sublining region of the rheumatoid joint is replete with blood vessels, which
are important for delivering inflammatory cells to the joint, such as monocytes and lymphocytes.
B)Extra-Articular Lesion
 Nonspecific inflammatory changes seen in blood
vessels(acute vasculitis) , lung
,pleura,pericardium,myocardium,lymph
nodes,peripheral nerves and eyes.
1. Skin (rheumatoid nodules)

 Most common cutaneous lesion

 Arise in region of the skin that are subjected to
pressure,including the ulnar aspect of the
forearm,elbows,occiput and lumbosacral area.
 Less common form in the
lungs,spleen,pericardium,myocardium,heart
valves,aorta and other viscera.
 Microscopically: the centre of nodule consist
of area of fibrinoid necrosis surrounded by a
prominent rim of epithelioid
histiocytes(activated macrophage) and
numerous lymphocytes and plasma cells.
A closer view showing the central necrosis on the left
side of the photomicrograph, with successive layers of Necrotizing granuloma surrounded by palisading histiocytes
palisading macrophages and lymphocytes (to the right and foreign body giant cell (black arrow)
of the necrosis).
Rheumatoid Nodules. Rheumatoid nodules commonly form near the extensor surface
of the elbow. They can be fixed to the underlying periosteum or can be freely mobile
2. Blood Vessels (Rheumatoid vasculitis)

 Developed in high risk in affected individuals with

severe erosive disease, rheumatoid nodules and
high titers of rheumatoid factors .
 Characterized by inflammatory destruction of small
and medium-sized blood vessels
 primarily due to leukocyte migration and resultant
damage.
 Development of red spots on the skin as a result.
 PATHOGENESIS
-The joint inflammation is immunologically mediated
- The initiating agent/s are not yet understood
- Proposed that it is initiated by activation of CD4+ helper
T cells
- The activated T cells produce cytokines that :-

a) Activate macrophages and other cells in the joint

space, releasing degenerative enzymes and other
factors that perpetuate inflammation..
b) Activate B cells, resulting in the production of
antibodies, some of which are directed against self-
antigens in the joint.

- The rheumatoid synovium is rich in both lymphocytes-

and-macrophage-derived cytokines.
- Activated T cells in RA lesions have also been shown
to express impressive amounts of cytokine called
RANK ligand .
• The role of antibodies in the disease is suspected
from a variety of experimental and clinical
observations .
• About 80% of patients have serum IgM ( and less
frequently IgG ) autoantibodies that bind to the Fc
portions of their own (self) IgG
• These autoantibodies are called rheumatoid factor
( RF )
• Genetic variables in the pathogenesis of RA are
suggested by the increased frequency of this
disease among first-degree relatives and a high
concordance rate in monozygotic twins
• There are also associations of HLA –DR4 and
polymorphism in the PTPN22 gene with RA
• There are elusive infectious agents whose antigens
may activate T or B cells.
Articular surface (top) shows loss of articular cartilage
beneath pannus overgrowth
The inflammation associated with RA can lead to
fibrosis (arrow) and fusion of the joint (ankylosis)
SYMPTOMS & SIGNS
• Come & go.
• Primarily affects joints, others are known
• When active several symptoms can be
acknowledged
- fatigue
- loss of energy
- lack of appetite
- muscle and joint aches
- stiffness
• During flares- joints frequently become red,
swollen, painful, and tender.
• In rheumatoid arthritis, multiple joints are usually
inflamed in a symmetrical pattern

• Occasionally, only one joint is inflamed.

• Chronic inflammation can cause damage to body

tissues, including cartilage and bone.

• is a systemic disease, its inflammation can affect

organs and areas of the body other than the joints.
DIAGNOSIS
• Imaging – x rays, ultrasound,MRI
• Stage I
• no damage seen on X-rays, although there may be signs of
bone thinning
• Stage II
• on X-ray, evidence of bone thinning around a joint with or
without slight bone damage

• abnormalities of soft tissue around joint possible

• Stage III
• on X-ray, evidence of cartilage and bone
damage and bone thinning around the joint
• joint deformity without permanent stiffening or
fixation of the joint
• extensive muscle atrophy
• abnormalities of soft tissue around joint
possible
• Stage IV
• on X-ray, evidence of cartilage and bone
damage and osteoporosis around joint
• joint deformity with permanent fixation of the
joint
• extensive muscle atrophy
• abnormalities of soft tissue around joint
possible

• Blood test
rheumatoid factor
sedimentation rate
TREATMENT
First-line medication
NSAIDs
• NSAIDs are medications that can reduce tissue
inflammation, pain, and swelling
• NSAIDs have side effects
• Example of NSAIDs – aspirin (acetylsalicylate)
Corticosteroid medications
• more potent than NSAIDs
• useful for short periods during severe flares of
disease activity or when the disease is not
responding to NSAIDs
• Have serious side
Second-line or "slow-acting" drugs
Disease-modifying anti-rheumatic drugs or
DMARDs

• These medicines may take weeks to months to

become effective.
• DMARDs can promote remission.
• Chemically synthesised DMARDs:

• azathioprine
• D-penicillamine
• gold salts
• methotrexate (MTX)
• sulfasalazine (SSZ)
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
Mortality
• Estimates of the life-shortening effect of RA vary;
most sources cite a lifespan reduction of 5 to 10
years
• RA sufferers suffer a doubled risk.