Rheumatoid Arthritis

Question 1

Define Rheumatoid Arthritis

Answer 1

Chronic autoimmune disease characterised by pain, stiffness and SYMMETIRCAL SYNOVITIS of synovial (diarthrial) joints

Question 2

When is the stiffness in the joints particularly bad in rheumatoid arthritis and what can make it better?

Answer 2

In the morning

It gets better with exercise

Question 3

What is a relatively common extra-articular manifestation of rheumatoid arthritis?

Answer 3

Rheumatoid nodules

Question 4

What causes the extra-articular manifestations of Rheumatoid arthritis?

Answer 4

Rheumatoid factor produces immune complexes that can go anywhere

Question 5

What type of antibody is the rheumatoid factor and where does t bind?

Answer 5

IgM antibody that binds to the Fc portion of IgG

Question 6

Is rheumatoid arthritis more common in males or females?

Answer 6

More common in females (3:1)

Question 7

What is the important genetic component that predisposes to Rheumatoid Arthritis?

Answer 7

The genetic component comes down to a specific set of amino acids within the beta chain of the DR molecule (amino acids 70-74 of the DR Beta1-chain)
This set of amino acids is conserved among all HLA subtypes that are associated with rheumatoid arthritis – it is called the shared epitope. HLA-DR4

Question 8

What important environmental factor can affect the susceptibility and severity of Rheumatoid Arthritis?

Answer 8

Smoking

Question 9

State some joints that are commonly affected in Rheumatoid Arthritis.

Answer 9

Metacarpophalangeal joint (MCP) 
Proximal interphalangeal joint (PIP) 
Wrists 
Knees 
Ankles 
Metatarsophalangeal joint (MTP)

Question 10

Name and describe two deformities that are indicative of Rheumatoid Arthritis.

Answer 10

Swan-neck deformity  
 Hyperextension of PIP
 Hyperflexion of DIP
Boutonniere deformity (button-like) 
 Hyperflexion at PIP

Question 11

Other that joints and around tendons, where else can synovium become inflamed?

Answer 11

Bursae –> Bursitis

Question 12

Why are rheumatoid nodules an important clinical finding?

Answer 12

Patients with rheumatoid nodules are always rheumatoid factor positive

Question 13

Where are rheumatoid nodules commonly seen?

Answer 13

Along the ulnar border

Question 14

What proportion of cases of Rheumatoid Arthritis is rheumatoid factor negative?

Answer 14

1/3

Question 15

Name another autoantibody that is very specific for Rheumatoid Arthritis.

Answer 15

Anti-cyclic citrullinated peptide antibody

Question 16

Which enzymes are responsible for the citrullination of peptides?

Answer 16

Peptidyl arginine deaminases (PADs

Question 17

Why do citrullinated peptide antigens develop in rheumatoid arthritis?

Answer 17

PADs are present in high concentrations in neutrophils and monocytes so there is increased citrullination of autologous peptides in inflamed synovium
Citrulline binds much better than arginine to the shared epitope (specific peptide sequence that is conserved in all MHC molecules that are associated with Rheumatoid Arthritis)
So Anti-CCP antibodies are more likely to develop in individuals with citrullinated autoantigens and those that have the shared epitope

Question 18

State some rare extra-articular manifestations of Rheumatoid Arthritis.

Answer 18

Vasculitis

Episcleritis

Question 19

What is the name given to the thickened, chronically inflamed synovial tissue in Rheumatoid Arthritis?

Answer 19

Pannus

Question 20

How thick is the normal synovial membrane?

Answer 20

It is normally almost a single cell lining

Question 21

Which cells are responsible for producing synovial fluid?

Answer 21

Synovial fibroblasts

NOTE: macrophages are also found within the lining

Question 22

Why is synovial fluid viscous?

Answer 22

It contains hyaluronic acid

Question 23

What type of collagen is present in articular cartilage?

Answer 23

Type 2 collagen

Question 24

What is the main proteoglycan in articular cartilage?

Answer 24

Aggrecan

Question 25

What three main things are responsible for the synovium becoming a proliferated mass (pannus)?

Answer 25

``` Neovascularisation Lymphangiogenesis Inflammatory cell recruitment:  Activated T and B cells  Plasma cells  Mast cells  Activated macrophages ```

Question 26

What are the three main cytokines involved in rheumatoid arthritis?

Answer 26

IL-1 IL-6 TNF-alpha

Question 27

What is the dominant cytokine and which cells produce it?

Answer 27

TNF-alpha | Produced by activated macrophages

Question 28

What class of drugs are commonly used in Rheumatoid Arthritis to modify the natural history of the disease?

Answer 28

Disease-modifying anti-rheumatic drugs (DMARDs)

Question 29

Describe the onset of action of DMARDs.

Answer 29

Slow onset and complex action

Question 30

Give some examples of DMARDs.

Answer 30

Methotrexate | Sulphasalazine

Question 31

What are the shortcomings of DMARDs?

Answer 31

They have significant adverse effects and require regular blood test monitoring

Question 33

Ant TNF antibodies

Answer 33

Infliximab

Question 34

What is the main treatment goal for Rheumatoid Arthritis with DMARDs?

Answer 34

Prevent joint damage and reduce synovial inflammation

Question 35

What is citrulination

Answer 35

conversion of arginine to citruline (not one of standard 20 amino acids) - a post translational modification

Question 37

What are the major risks with biological therapy?

Answer 37

EXPENSIVE All biological therapies are associated with an increase infection risk TNF-alpha inhibition is associated with increased susceptibility to mycobacterial infections (TUBERCULOSIS)