Rheumatoid Arthritis

Question 1

Define Rheumatoid Arthritis

Answer 1

Chronic autoimmune disease characterised by pain, stiffness and SYMMETRICAL SYNOVITIS of synovial joints.

Question 2

What are the Key features of RA?

Answer 2

Key Features

1. Symmetrical
2. POLYarthritis
3. Early morning stiffness
4. Joint damage and destruction

Question 3

What are the Extra-Articular Features of RA?

Answer 3

Extra-Articular Features

1. Rheumatoid nodules
2. RARE: vasculitis, episcleritis
3. Rheumatoid Factor may be detected in the blood

Question 4

What are the Associations and Risk factors of RA?

Answer 4

Associations and Risk Factors

1. 3 x more common in FEMALES
2. Genetics – a specific sequence of amino acids within the beta chain of the HLA-DR molecule is conserved among all HLA subtypes associated with RhA – Shared Epitope
3. Smoking – increases susceptibility and severity of disease

Question 5

What is the structure of the Synovium, what cells can be found in the synovial fluid, what makes it viscous?

What is the main preteoglycan of articular cartilage?

From what is the articular cartilage composed of?

Answer 5

Synovium

1. Almost single cell lining
2. Macrophages and fibroblasts are found within the synovial lining – these produce synovial fluid
3. Hyaluronic acid makes the synovial fluid viscous
4. Articular cartilage = type 2 collagen
5. Main proteoglycan of articular cartilage = aggrecan

Articular Cartilage Composition

• The most important component is a proteoglycan called AGGRECAN
• Aggrecan is good at drawing water into the articular cartilage
• Aggrecan consists of chondroitin sulfate and keratan sulfate chains
• Breakdown of proteoglycans leads to the mechanical properties of the joint being compromised
• Hyaluronic acid is found in the synovial fluid and is responsible for its viscosity

Question 6

What is the affected site of RA?

Answer 6

Affected Sites

• The SYNOVIUM is the main site of pathology

Autoimmune inflammation of the synovium

The synovium becomes a proliferated mass (pannus) due to neovascularisation and lymphangiogenesis

• Synovium is found in THREE main places:
  
  1. Synovial joints
  2. Tenosynovium (surrounding tendons)
  3. Bursa (pockets of fluid found on joint surfaces)

The synovial membrane becomes thickened and chronically inflamed

The inflammation leads to erosion of adjacent cartilage and bone

Question 7

What are the main Defrormities that are seen in RA?

Answer 7

1. Swan-neck Deformity
   
   • Hyperextension of PIP
   • Hyperflexion of DIP
2. Boutonniere Deformity
   
   • Hyperflexion of PIP

Question 8

What are the main deteminants that cause inflammation in RA?

Answer 8

Antibodies:

Rheumatoid Factor

• IgM antibody that binds to Fc portion of IgG
• NOT a diagnostic test for RhA
• 1/3 of rheumatoid arthritis is RF negative

Anti-cyclic Citrullinated Peptide Antibodies

• HIGHLY SPECIFIC for RhA
• Peptides get citrullinated by peptidyl arginine deaminases (PADs)
• PADs are found in high concentrations in neutrophils and monocytes
• So, there is increased citrullination of self-peptides in inflamed synovium
• Anti-CCP is associated with smoking and HLA shared epitope
• Explanation: citrulline binds better than arginine to the peptide sequence that is conserved in all MHC molecules associated with RhA

Cytokines

Inflammation results in a cytokine imbalance. Key cytokines involved:

1. IL-1
2. IL-6
3. TNF-a – MAIN CYTOKINE

Question 9

What is the main treatment?

Answer 9