Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and systemic symptoms. It affects around 1-3% of the population, occurring more frequently in women between ages 30-50. RA causes periods of disease flares and remissions. The synovium becomes engorged with new blood vessels and inflammatory cells. Genetic and environmental factors may contribute to disease development. Diagnosis involves assessing symptoms of joint pain and stiffness as well as blood tests for rheumatoid factor and anti-CCP antibodies. Treatment includes NSAIDs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologic medications to reduce inflammation and prevent further joint damage.

1. RHEUMATOID ARTHRITIS
Lasha Chkhikvadze USMD 2024

2. Definition
• Rheumatoid arthritis (RA) is a chronic
usually progressive inflammatory
disorder of unknown etiology
characterized by joint involvement and
systemic manifestations. So it is a
systemic autoimmune disease.
• It affects approximately 1-3% of the
world population
• Occurs 3 times more in women
• peaks at age 30-50 years

3. o RA is characterized by periods of disease flares
and remissions
o Synovium is engorged with new blood vessels
and inflammatory cells
o Multiple joints are often affected in the
symmetric manner
It is a systemic disease
but most characteristic lesions
are seen in the synovium or
within Rheumatoid nodules

4. • Multiple joints:
• Usually >5
• Symmetrical
• MC small joints:
Metacarpophalangeal,
proximal interphalangeal,
metatarsophalangeal
• As disease worsens:
• Large joints:
Shoulders,
elbow,
knees,
ankles
• Flares – sudden worsening: swelling, warmth, redness,
pain.
• Stiffness – especially in the morning or being inactive for
a long time
• Specific deformities of the joints

5. Causes and predisposing factors
40%
• HLA-DR1 & HLA-DR4
genes
• Genes encoding: TNF a
and heat shock proteins
• Genes encoding collagen
II
• Gender
• Familial
• Trauma
• Pathogens
• Cigarette smoke

6. • Citrullination of
arginine in
Collagen II and
Vimentin
• Recognition by
APCs – HLA-DR4 &
HLA-DR1a

7. • T cells in the joints release – IFN-y and IL-17 to recruit
synovial macrophages and fibroblasts
• RankL binds Rank on osteoclasts to initiate bone degradation
• Macrophages release – TNF-a, IL- 1, IL-6 to increase
inflammation and stimulate angiogenesis and synovial cells
to proliferate
• Pannus – thick, swollen synovial membrane with granulation
tissue (fibroblasts, myofibroblasts, inflammatory cells)
• Overtime pannus damages cartilage, soft tissue, bone.
Lymphoid neogenesis in the secondary follicles in
the synovium

8. • Anti-CCP – anti cyclic citrullinated
peptide – useful for testing
• Rheumatoid factor – auto-antibody
against the self – IgM antibodies
against the Fc portion of altered IgG
(cryptic epitopes)
Immune complexes activate complement system

9. Systemic complications
• Brain – Il-1, IL-6 act as pyrogens inducing
fever
• Skeletal muscle – protein breakdown
• Skin – rheumatoid nodules
• Blood vessels – vasculitis
(atherosclerosis)
• Liver – releases hepcidin – decreases
iron level by inhibiting absorption -
anemia
• Lung – activation of fibroblasts – scar
tissue – decrease gas exchange + pleural
effusion

10.  Rheumatoid factor – is found in 60% of patients with RA. However as
many as 5% of healthy individuals will have elevated titers of RF. If
initially negative, the test can be repeated in 6-12 months. RF is not an
accurate measure of disease progression.
 Anti-CCP – found in most patients with RA and are useful in predicting
erosive disease.
 Erythrocyte sedimentation rate and C-reactive protein – they are
markers of inflammation and are usually elevated in patients with RA.
They can also help to indicate the activity of the disease, but they do
not indicate disease severity.
 Radiographic examination

11. Drug
classes
NSAID corticosteroids DMARD biologics
Mechanis
m of action
NSAIDs inhibit the generation of
prostaglandins by blocking
cyclooxygenase enzymes, COX-1 and
COX-2.
inhibit the synthesis of
multiple inflammatory
proteins through
suppression of the genes
that encode them.
inhibition of an
enzyme involved in the
metabolism of folic
acid, dihydrofolate
reductase
Supress T/B cells,,
Block TNF-a
Block IL-1.6
effect reduce acute inflammation thereby
decreasing pain and improving function
anti-inflammatory and
immunoregulatory
activity
only DMARD agents have
been shown to alter the
disease course and
improve radiographic
outcomes
Additional
notes
these drugs alone do not change the
course of the disease of rheumatoid
arthritis or prevent joint destruction.
Corticosteroids are useful
in early disease as
temporary adjunctive
therapy while waiting for
DMARDs to exert their
antiinflammatory effects.
However the dose required
to achieve a response is
variable in individual patients
and may require 4-6 weeks
after a dose increase to
determine if the drug is
working.
Onset of
action
short short Long (weeks-months) long
Treatment

12. Thank you!