Lecture 6 - RA - finished

Question 1

Define rheumatoid arthritis

Answer 1

A chronic autoimmune disease characterised by progressive arthritis of several small to medium sized joints, especially in the hands and a range of systemic manifestations

Question 2

Epidemiology RA

Answer 2

W:M = 1.6:1
Most common inflammatory arthridity
>55yoa /3rd and 4th decade

Question 3

Typical features of RA

Answer 3

RAndy Typically Fucks MATES

• Morning stiffness
• Appearance of anti-IgG globulins (Rheumatoid factors).
• Tenosynovitis
• increased ESR
• Symmetrical polyarthritis

Question 4

AETIOLOGY OF RA

Answer 4

RAndy is affected Constantly by Humiliating Genital Infections

GENETIC FACTORS:
Increased risk associated with presence of HLA-DR4
- found in 70% causasians with RA
- found in 25% of general pop.

INFECTIOUS AGENTS:
Bacteria (usually gram negative)
Mycoplasmas
Viruses
- EBV is a polyclonal B-cell activator that stimulates RF production
- EBV has been isolated from the joints of RA patients

HUMORAL IMMUNITY
- 80% of RA patients have RF
RF is an abnormal IgM which attack the FC portion of the hosts IgG antibodies.
RF and immune complex - deposit in the synovium and articular cartilage leading to complement activation
Complement activation leads to chemotaxis of neutrophils and local inflammatory cells as well as local inflammatory mediator stimulation
RF in joints and circulation results in acute and chronic inflammatory effects in joints and organs.

CELLULAR IMMUNITY
T helper cells are abnormally regulated and activate macrophages against the bodys own cells, causing the release of cytokines. The cytokines activate fibroblasts, chondrocytes and synovial cells. This results in the release of destructive enzymes and cellular proliferation/

Question 5

RA PATHOLOGY outline and stages (literally list the stages)

Answer 5

Joint and tendon pathology:

• Stage 1: Synovitis
• Stage 2: Destruction
• Stage 3: Deformity

Extra-articular pathology

Question 6

RA PATHOLOGY

STAGE 1

Answer 6

RAndy in stage one of his Sex with Mates cure, he has to wear VESTS

STAGE 1: SYNOVITIS
Early changes:
Synovitis
- synovial infiltration by lymphocytes and plasma cells
- neovascularisation
- proliferation of synoviocytes

Thickening of capsular structures

Villous formation of the synovium (growth factors released by macrophages induce synovial hyperplasia and granulation tissue proliferation)

Effusion into the joint and tendon sheaths

SSX = pain, swelling and tender

Question 7

PATHOLOGY OF RA

STAGE 2

Answer 7

RAndy in stage 2 of his cure must destroy reputation: persistent immitations of JT BATS away women.

STAGE 2: DESTRUCTION
Persistent inflammation results in joint and tendon destruction.

Bone erosion: due to
- pannus invasion and osteoclastic resorption.

Articular cartilage erosion: due to

• proteolytic enzymes
• vascular tissue in folds of synovial tissue
• invasion by pannus which spreads over the articular cartilage

Tendon sheath: similar changes as cartilage and bone

• tenosynovitis
• invasion of collagen bundles by inflam. elements causing tendon rupture

Synovial effusion:
= increased amounts of fibrinoid tissue causing swelling of joints/ tendons/ bursae
= blood vessel proliferation

Question 8

PATHOLOGY OF RA

STAGE 3

Answer 8

RAndy in stage 3 of his cure must DEFORM himself: progressively IDentifitying himself as a CAT

STAGE 3: DEFORMITY
Progressive instability and deformity of joints resulting in:
- articular destruction
- capsular stretching
- tendon rupture

Inflammation has often subsided and patients symptoms are due to joint deformation

Question 9

PATHOLOGY OF RA

EXTRA ARTICULAR

Answer 9

RAndys Extra Leg Room in his VV (V double) Makes Sense

EXTRA-ARTICULAR MANIFESTATIONS:
Rheumatoid nodules:
Small granlomatous lesions consisting of
- central necrotic zone
- surrounding enclosure of local histiocytes
- surrounding inflammatory granulation tissue
Rheumatoid nodules can be found in the synovium, on tendons, on sclera, in viscera, and under the skin esp over body prominences.

Lymphoid tissue hyperplasia
Vasculitis
Muscle weakness -  may be due to:
- rheumatoid myopathy
- neuropathy 
- SC involvement
Sensory changes
Visceral disease: e.g. lungs, kidney, heart, brain, GIT

Question 10

What is a rheumatoid nodule?

Answer 10

• small subcutaneous lumps
• rubbery
• are pathognomonic of RA
• are in 25% of RA patients

Small granulomatous lesions consisting of

• central necrotic zone
• surrounding enclosure of local histiocytes
• surrounding inflammatory granulation tissue

Rheumatoid nodules can be found in the synovium, on tendons, on sclera, in viscera, and under the skin esp over body prominences.

Question 11

What is the typical presentation for RA

Answer 11

• females 30-40 years
• complaining of pain (acute), swelling, loss of mobility in proximal joints of fingers
• previous history of muscle pain, tiredness, weight loss, general lack of well being

Question 12

What are the symptoms of RA?

Answer 12

EARLY:
• polysynovitis
• soft tissue swelling
• stiffness: classically is generalised of occurring after periods of inactivity e.g. rising from bed in the morning

LATE:
With time the clinical manifestations appear in other joints:
• wrists most frequent
• feet
• knees
• shoulders

Question 13

What are the signs of RA?

Answer 13

EARLY:
Symmetrically distributed swelling and tenderness of the:
• MCP's 
• PIP's 
• wrists

Tenosynovitis in:
• extensor compartments of wrists
• flexor sheaths of fingers
 ** indicated clinically by:
• tenderness (over dorsum of wrist/palm)
• crepitation (during passive ROM)

Larger joints we see:
• local warmth
• intra articular effusion
• synovial hypertrophy
• joints are mobile and not deformed

LATER:
Increasing joint deformity
Constant ache
Joint instability and tendon rupture:
- results in the typical rheumatoid deformities such as:
∗ ulnar deviation of fingers
∗ radial and palmar displacements of wrists
∗ valgus knees
∗ valgus feet
∗ clawed toes
Joint movement is restricted and usually painful.
1/3 of patients develop cervical spine pain.

Question 14

RA RADIOLOGICAL MANIFESTATIONS:

Answer 14

EARLY
XR’s show changes consistent with synovitis ie
• soft tissue swelling
• periarticular osteoporosis

LATER
• marginal bone erosions
• narrowing of articular space (esp. in the proximal joints of hands/feet).

ADVANCES
• articular destruction
• joint deformity
• subluxation of atlanto-axial or mid cervical levels.

Radiol:
Rat bite lesion - usually in bare area
Juxta-articular osteopoenia
Pseudocysts
Soft tissue swelling
Subchondral sclerosis
Symmetrical joint space loss

Question 15

Diagnostic Criteria For RA

Answer 15

RAndy was diagnosed by Morning Stiffies And A Stuffed Room Rammed Full of Radios

1. morning stiffness
2. arthritis of 3 or more joints areas
3. arthritis of hand joints
4. symmetric arthritis
5. rheumatoid nodules
6. positive serum rheumatoid factor
7. Radiographic changes

In order to diagnose RA using the above criteria we must have:

a. any 4 of the above criteria present
b. criteria 1-4 must be present for more than 6 weeks