Rheumatoid arthritis

RHEUMATOID ARTHRITIS

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.

• 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.

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.

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.

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.

• 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.

BILAT RH. NODULES

RH.NODULE

Rh. nodule

Rh nodule

• 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.

• 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.

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,

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.

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.

• 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).

3) GENETIC SUSCEPTIBILITY:

- Well defined familial predisposition

- High rate of concordance b/w monozygotic twins

- Class II HLA locus (HLA DRB1*0401 & *0404 alleles).

4) ANTIGENS :

- Not known

- Microbial antigens are a possibility but their role is not confirmed.

- PTPN22 (Protein tyrosine phosphatase)→ effects the T-cells.

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.

• 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.

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.

• 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,

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.

COMPLICATIONS

• Systemic amyloidosis.

• Vasculitis (aorta).

• Iatrogenic: GIT bleeding due to NSAIDs.

• Infections ass with ch. steroid use.

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)

• FELTY’S SYNDROME:

RA associated with splenomegaly & hypersplenism & consequently haematological derangements.

h/e :Pannus

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).

ANKYLOSING SPONDYLOARTHRITIS

• Rheumatoid spondylitis

• Axial joints esp. sacroiliac joint

• 2nd & 3rd decade

• 90% HLA-B27 associated

• Low backache

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

PSORIATIC ARTHRITIS

• 10% of pt. with psoriasis

INFECTIOUS ARTHRITIS

• Hematogenous• Direct inoculation• From contiguous spread• Types1. Suppurative2. Tuberculous3. Lyme 4. Viral