Rheumatoid arthritis

1. RHEUMATOID ARTHRITIS

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 : 4
th
– 7
th
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.

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.

9. BILAT RH. NODULES

10. RH.NODULE

11. Rh. nodule

12. Rh nodule

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
1
st
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.

26. COMPLICATIONS
•Systemic amyloidosis.
•Vasculitis (aorta).
•Iatrogenic: GIT bleeding due to NSAIDs.
•Infections ass with ch. steroid use.

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.

37. h/e :Pannus

38. SERONEGATIVE
SPONDYLOARTHROPATHIES
•Develop in genetically predisposed
individuals
•Immune mediated
•HLA-B27 associated
•Eg Ankylosing spondylitis
Reactive arthritis
Psoriatic arthritis
Arthritis associated with IBD
(inflam. bowel disease).

39. ANKYLOSING
SPONDYLOARTHRITIS
•Rheumatoid spondylitis
•Axial joints esp. sacroiliac joint
•2
nd
& 3
rd
decade
•90% HLA-B27 associated
•Low backache

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

41. PSORIATIC ARTHRITIS
•10% of pt. with psoriasis

42. INFECTIOUS ARTHRITIS
•Hematogenous
•Direct inoculation
•From contiguous spread
•Types
1.Suppurative
2.Tuberculous
3.Lyme
4.Viral