Rheumatoid Arthritis

Question 1

Why are rheumatoid nodules an important clinical finding?

Answer 1

Patients with rheumatoid nodules are always rheumatoid factor positive

Question 2

Where are rheumatoid nodules commonly seen?

Answer 2

Along the ulnar border

Question 3

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

Answer 3

1/3

Question 4

Name another autoantibody that is very specific for Rheumatoid Arthritis.

Answer 4

Anti-cyclic citrullinated peptide antibody

Question 5

Which enzymes are responsible for the citrullination of peptides?

Answer 5

Peptidyl arginine deaminases (PADs

Question 6

Why do citrullinated peptide antigens develop in rheumatoid arthritis?

Answer 6

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 7

State some common extra-articular manifestations of Rheumatoid Arthritis.

Answer 7

Rheumatoid nodules Fever Weight loss

Question 8

State some rare extra-articular manifestations of Rheumatoid Arthritis.

Answer 8

Vasculitis Episcleritis Neuropathies Amyloidosis Lung disease (nodules, fibrosis, pleuritis) Felty’s syndrome (triad of splenomegaly, leukopenia and rheumatoid arthritis)

Question 9

What is an early radiographic abnormality in Rheumatoid Arthritis?

Answer 9

Juxta-articular osteopenia

Question 10

What are some later radiographic abnormalities in Rheumatoid Arthritis?

Answer 10

Joint erosion and, subsequently, joint destruction and deformity

Question 11

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

Answer 11

Pannus

Question 12

Which area of bone tends to be eroded first in Rheumatoid Arthritis?

Answer 12

Bare area of bone – this is within the synovial membrane but is not covered by articular cartilage (periarticular erosion)

Question 13

How thick is the normal synovial membrane?

Answer 13

It is normally almost a single cell lining

Question 14

Which cells are responsible for producing synovial fluid?

Answer 14

Synovial fibroblasts NOTE: macrophages are also found within the lining

Question 15

Why is synovial fluid viscous?

Answer 15

It contains hyaluronic acid

Question 16

What type of collagen is present in articular cartilage?

Answer 16

Type 2 collagen

Question 17

What is the main proteoglycan in articular cartilage?

Answer 17

Aggrecan

Question 18

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

Answer 18

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

Question 19

What are the three main cytokines involved in this disease process?

Answer 19

IL-1 IL-6 TNF-alpha

Question 20

What is the dominant cytokine and which cells produce it?

Answer 20

TNF-alpha Produced by activated macrophages

Question 21

What is the main treatment goal for Rheumatoid Arthritis?

Answer 21

Prevent joint damage

Question 22

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

Answer 22

Disease-modifying anti-rheumatic drugs (DMARDs)

Question 23

When are glucocorticoids used and why are they not used long term?

Answer 23

They are used in the short-term to control, for example, exacerbation of the disease They are not used long-term because of their large side effect profile

Question 24

Describe the onset of action of DMARDs.

Answer 24

Slow onset and complex action

Question 25

Give some examples of DMARDs.

Answer 25

Methotrexate Sulphasalazine Hydroxychloroquine Leflunomide Gold Penicillamine

Question 26

What are the shortcomings of DMARDs?

Answer 26

They have significant adverse effects and require regular blood test monitoring

Question 27

What are the major risks with biological therapy?

Answer 27

EXPENSIVE All biological therapies are associated with an increase infection risk TNF-alpha inhibition is associated with increased susceptibility to mycobacterial infections (TUBERCULOSIS) So all patients must be screened for TB before starting treatment B cell depletion is associated with HEPATITIS B activation so patients need to be screened for this as well B cell depletion is also associated with JC virus infection and progressive multifocal leukoencephalopathy (PML) – RARE