Rheumatoid Arthritis

Question 1

Define Rheumatoid Arthritis

Answer 1

Chronic AI disease characterised by pain, stiffness + SYMMETIRCAL SYNOVITIS of synovial (diarthrial) joints

Question 2

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

Answer 2

Rheumatoid nodules

Question 3

What causes the extra-articular manifestations? What are 2 rarer extra-articular manifestations?

Answer 3

Rheumatoid factor produces immune complexes that can go anywhere
Vasculitis
Episcleritis

Question 4

What type of antibody is the rheumatoid factor?

Answer 4

IgM autoantibody that binds to the Fc portion of IgG

Question 5

Is rheumatoid arthritis more common in males or females?

Answer 5

More common in females (3:1)

Question 6

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

Answer 6

Specific set of AA’s (70-74) within the beta chain of the HLA-DR binding groove
This set of AA’s is conserved among all HLA subtypes that are associated with RA = the shared epitope

Question 7

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

Answer 7

Smoking

Question 8

State 6 joints that are commonly affected in Rheumatoid Arthritis.

Answer 8

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

Question 9

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

Answer 9

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

Question 10

Describe the appearance of extensor tenosynovitis.

Answer 10

Swelling around the extensor tendon that is inflamed

When the fingers are extended, the swelling will move showing the inflammation is around the tendon + not the joint

Question 11

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

Answer 11

Bursae –> Bursitis

Question 12

What are sub-cutaneous nodules?

Answer 12

Central area of fibrinoid necrosis surrounded by histiocytes + a peripheral layer of connective tissue

Question 13

Why are rheumatoid nodules an important clinical finding?

Answer 13

Patients with rheumatoid nodules are always rheumatoid factor positive

Question 14

Where are rheumatoid nodules commonly seen?

Answer 14

Along the ulnar border of the forearm

Question 15

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

Answer 15

1/3

Question 16

Name another autoantibody that is very specific for Rheumatoid Arthritis.

Answer 16

Anti-cyclic citrullinated peptide antibody

Question 17

Which enzymes are responsible for the citrullination of peptides?

Answer 17

Peptidyl arginine deaminases (PADs)

Question 18

Why do citrullinated peptide antigens develop in rheumatoid arthritis?

Answer 18

PADs are present in high concentrations in neutrophils + monocytes so there is increased citrullination of autologous peptides in inflamed synovium
Citrulline binds much better than arginine to the shared epitope
Anti-CCP antibodies are more likely to develop in individuals with citrullinated autoantigens (e.g. smokers)+ those that have the shared epitope

Question 19

State 3 common extra-articular manifestations of Rheumatoid Arthritis.

Answer 19

Subcutaneous nodules
Fever
Weight loss

Question 20

State 6 rare extra-articular manifestations of Rheumatoid Arthritis.

Answer 20

Vasculitis
Episcleritis (ocular inflammation)
Neuropathies
Amyloidosis
Lung disease (nodules, fibrosis, pleuritis)
Felty’s syndrome (triad of splenomegaly, leukopenia + RA)

Question 21

What is an early radiographic abnormality in Rheumatoid Arthritis?

Answer 21

Juxta-articular osteopenia

Question 22

What are some later radiographic abnormalities in Rheumatoid Arthritis?

Answer 22

Joint erosion at margins of joint

Subsequent joint destruction + deformity

Question 23

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

Answer 23

Pannus

Question 24

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

Answer 24

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

Question 25

How thick is the normal synovial membrane?

Answer 25

~ single cell lining

Question 26

Which cells are responsible for producing synovial fluid?

Answer 26

``` Synovial fibroblasts (Synoviocytes) Macrophage like cells are also found within the lining ```

Question 27

Why is synovial fluid viscous?

Answer 27

It contains hyaluronic acid

Question 28

What type of collagen is present in articular cartilage?

Answer 28

Type 2 collagen

Question 29

What is the main proteoglycan in articular cartilage?

Answer 29

Aggrecan

Question 30

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

Answer 30

Neovascularisation Lymphangiogenesis Inflammatory cell recruitment: (Activated T + B cells, Plasma cells, Mast cells, Activated macrophages)

Question 31

What are the three main cytokines involved in Rheumatoid arthritis?

Answer 31

IL-1 IL-6 TNF-alpha

Question 32

What is the dominant cytokine and which cells produce it?

Answer 32

TNF-alpha | Produced by activated macrophages

Question 33

What is the main treatment goal for Rheumatoid Arthritis?

Answer 33

Prevent joint damage

Question 34

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

Answer 34

Disease-modifying anti-rheumatic drugs (DMARDs)

Question 35

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

Answer 35

Used in the short-term to control, e.g. control flare of disease Not used long-term because of their large side effect profile

Question 36

Describe the onset of action of DMARDs.

Answer 36

Slow onset + complex action

Question 37

Give 3 examples of DMARDs.

Answer 37

Methotrexate Sulphasalazine Hydroxychloroquine

Question 38

What are the shortcomings of DMARDs?

Answer 38

All have significant adverse effects + require regular blood test monitoring

Question 39

What are 5 major risks with biological therapy?

Answer 39

Expensive All associated with an increase infection risk TNF-alpha inhibition is associated with increased susceptibility to mycobacterial infections: TUBERCULOSIS- patients must be screened for TB before starting treatment) B cell depletion is associated with HEPATITIS B reactivation so patients need to be screened for this B cell depletion is also associated with JC virus infection + progressive multifocal leukoencephalopathy (PML), RARE

Question 40

List 4 key features of rheumatoid arthritis

Answer 40

Chronic Polyarthritis Symmetrical Early morning stiffness in + around joints

Question 41

Describe the character of the swellings in rheumatoid arthritis

Answer 41

Soft on palpation

Question 42

List 4 examples of biological therapy for rheumatoid arthritis

Answer 42

Inhibition of tumour necrosis factor alpha (TNF alpha) B cell depletion Modulation of T cell co-stimulation Inhibition of IL6