rheumatoid arthritis
TRANSCRIPT
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RHEUMATOID ARTHRITIS
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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.
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• 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.
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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.
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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.
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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.
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• 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.
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BILAT RH. NODULES
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RH.NODULE
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Rh. nodule
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Rh nodule
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• 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.
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• 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.
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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,
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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.
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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.
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• 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).
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3) GENETIC SUSCEPTIBILITY:
- Well defined familial predisposition
- High rate of concordance b/w monozygotic twins
- Class II HLA locus (HLA DRB1*0401 & *0404 alleles).
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4) ANTIGENS :
- Not known
- Microbial antigens are a possibility but their role is not confirmed.
- PTPN22 (Protein tyrosine phosphatase)→ effects the T-cells.
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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.
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• 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.
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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.
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• 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 contentC) 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,
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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.
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COMPLICATIONS
• Systemic amyloidosis.
• Vasculitis (aorta).
• Iatrogenic: GIT bleeding due to NSAIDs.
• Infections ass with ch. steroid use.
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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)
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• FELTY’S SYNDROME:
RA associated with splenomegaly & hypersplenism & consequently haematological derangements.
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h/e :Pannus
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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).
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ANKYLOSING SPONDYLOARTHRITIS
• Rheumatoid spondylitis
• Axial joints esp. sacroiliac joint
• 2nd & 3rd decade
• 90% HLA-B27 associated
• Low backache
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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
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PSORIATIC ARTHRITIS
• 10% of pt. with psoriasis
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INFECTIOUS ARTHRITIS
• Hematogenous• Direct inoculation• From contiguous spread• Types1. Suppurative2. Tuberculous3. Lyme 4. Viral