2. RHEUMATOID ARTHRITIS
• Chronic systemic inflammatory disorder
that may affect many tissues & organs-
skin, BVs, heart, lungs & muscles- but
principally attacks the JOINTS, producing
nonsuppurative proliferative &
inflammatory synovitis that often
progresses to destruction of articular
cartilage & ankylosis of joints.
3. • 5% of world’s population is afflicted by RA.
• Male to female ratio 1:3.
• Age : 4th
– 7th
decade but no age is
immune.
• Cause not known but AUTOIMMUNITY
plays a major role in its pathogenicity.
4. MORPHOLOGY
• JOINTS:
1): SYNOVIUM (gross) becomes bulky,
edematous, thickened, congested &
hyperplastic.
2): Normal smooth contour is transformed→
formation of fronds & villi.
3): (microscopy): Infiltration of synovium by
dense perivascular inflammatory infiltrate
consisting of B cells & CD4+ helper T cells,
plasma cells & macrophages with formation of
lymphoid follicles.
5. 4): Increased vascularity due to vasodilation
& angiogenesis with hemosiderin deposits.
5): Aggregation of organizing fibrin covering
synovium & floating in joint space as rice
bodies.
6): Accumulation of neutrophils in synovial fluid
& superficial synovium.
7): Osteoclastic activity in underlying bone
→synovium penetrating into bone→ juxtra-
articular erosions, subchondrial cysts, &
osteoporosis.
8): Pannus formation.
6. PANNUS : mass of synovium & synovial stroma
consisting of inflammatory cells, G.T, &
fibroblasts.
- Grows over articular cartilage & causes its
erosion.
- Pannus bridges the apposing bones forming
fibrous ankylosis which ossifies resulting in
bony ankylosis.
- Inflammation in adjacent tendons, ligaments, &
skeletal muscles is common.
7.
8. • SKIN:
RHEUMATOID NODULES : seen in 25% of pt.
Arise in regions subjected to pressure like ulnar
aspect of forearm, elbows, occiput &
lumbosacral areas.
Also formed in lungs, spleen, pericardium,
myocardium, valves, aorta,
Firm, nontender, round to oval within
subcutaneous tissue
M/E: central zone of fibrinoid necrosis surrounded
by a rim of epithelioid histiocytes, lymphocytes
& plasma cells.
13. • BLOOD VESSELS:
VASCULITIS (is a potentially bad prognostic
indicator of RA).
* Medium to small arteries are involved like PAN
(kidney bv are not involved).
* Vasa nervorum & digital arteries are obstructed
by endarteritis obliterans resulting in neuropathy,
ulcers, & gangrene
* Venulitis produces purpura, ulcers, nail bed
infarction.
14. • BV are involved in severe disease with
rheumatoid nodules & high levels of RF
• It is potentially catastrophic complication
of RA particularly when it affects vital
organs.
15. PATHOGENESIS
• Autoimmune disease due to exposure of
genetically susceptible host to an
unknown arthritogenic antigen.
• Therefore, key considerations in
pathogenesis are :-
1) Nature of autoimmune reaction,
2) Mediators of tissue injury,
3) Genetic susceptibility,
4) Arthritogenic antigen,
16. 1) AUTOIMMUNE REACTION:
Consists of ACTIVATED CD4+ T cells & B
LYMPHOCYTES:
• Target antigens & how these lymphocytes are
initiated is not known.
• T-cells stimulate other cells in joint to produce
cytokines.
• Role of B cells is controversial but immune
complex deposition play some role in joint
destruction.
17. 2) MEDIATORS OF JOINT INJURY:
- CYTOKINES play pivotal role & imp. ones are
TNF & IL-1.
- Secreted by macrophages & synovial cells
activated by T cells in the joint.
- TNF & IL-1 in turn, stimulate synovial cells to
proliferate & produce various mediators (PG) &
matrix metalloproteinases (MMPs) causing
cartilage destruction.
18. • T cells & synovial fibroblasts also
produce RANKL which activate
osteoclasts & promotes bone
destruction.
• Net result is hyperplastic synovium with
inflammatory cells forming pannus→
sustained, irreversible cartilage
destruction & erosion of subchondral
bone.
• Anticytokine therapy (esp against TNF).
19. 3) GENETIC SUSCEPTIBILITY:
- Well defined familial predisposition
- High rate of concordance b/w
monozygotic twins
- Class II HLA locus (HLA DRB1*0401 &
*0404 alleles).
20. 4) ANTIGENS :
- Not known
- Microbial antigens are a possibility but
their role is not confirmed.
- PTPN22 (Protein tyrosine
phosphatase)→ effects the T-cells.
21. CLINICAL COURSE of RA.
• Variable, slow, insidious disease.
• Malaise, fatigue, & generalized musculoskeletal
pain.
• 10% have acute onset.
• Small joints are affected before larger ones.
MCP, PIP,MTP, IP joints followed by wrist,
ankles, & knee.
• Cervical spine also affected.
• Hip jt rarely affected (only late in course of
disease).
• Typically sparing of lumbosacral region.
22. • Swollen, painful, morning stiffness.
• Disease may be slow or rapid &
fluctuates over period of years with
periods of partial or complete
remission.
• Maximum damage occurs during the
1st
4 -5 yrs.
• X-rays: Juxta-articular osteopenia,
bone erosion with narrowing of joint
space from loss of articular cartilage.
23. CHARACTERISTIC GROSS
DEFORMITIES:
• Radial deviation of wrist.
• Ulnar deviation of fingers.
• Flexion-hyperextension of fingers (swan
neck).
• Bakers cyst (large synovial cysts) in post
knee due to ↑ intraarticular pressure.
24. • LABORATORY TESTS:
A) Rheumatoid factor (RA factor): IgM antibody but this is
not diagnostic as it may appear in many other conditions.
B) Synovial fluid: - neutrophils
- high protein content
- low mucin content
C) Diagnosis is made if 4 of following criteria are present:
1: Morning stiffness,
2: Arthritis in 3 or more joints areas.
3: Arthritis of hand joints,
4: Symmetric arthritis,
5: Rheumatoid nodules,
6: Serum rheumatoid factor,
7:Typical radiographic changes,
25. RHEUMATOID FACTOR
• IgM antibody against Fc fragment of
patients own IgG present in 80%
(seropositive).
• Ag-Ab complexes present in circulation &
in synovial fluid.
• RF titres raised in: viral hepatitis, cirrhosis,
sarcoidosis, & leprosy.
27. VARIANT OF RA (STILL DISEASE)
• JUVENILE RA (JRA) or STILL’S DISEASE
- Before the age of 16.
- Arthritis for minimum of 6 wks.
- Male: Female ratio is 1:2.
JRA DIFFERS FROM RA IN FOLLOWING WAYS:
• Oligoarthritis (involvement of 5 joints).
• Systemic onset is more common.
• Large joints (knees, wrists,elbows, & ankles).
• RN (rh. nodules) & RA are usually absent.
• ANA is common.
• Extra-articular manifestations more common
(pericarditis, myocarditis, uveitis, pul fibrosis, GN,
growth retardation)
28. • FELTY’S SYNDROME:
RA associated with splenomegaly &
hypersplenism & consequently
haematological derangements.
40. REACTIVE ARTHRITIS
• Noninfectious arthritis of appendicular
skeleton occurring within one month of primary
inf. localized elsewhere in body
• Usually genitourinary & GIT Infections
• Chlymadia
• Shigella, salmonella, yersinia, campylobacter
• Triad of arthritis, nongonococcal urethritis or
cervicitis, conjunctivitis is called Reiter
syndrome
