Rheumatoid arthritis

Question 1

What is rheumatoid arthritis?

Answer 1

Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of synovial membrane) of synovial joints

Question 2

What is a key identifying feature of arthritis?

Answer 2

It is symmetrical

Question 3

How do patients with rheumatoid arthritis tend to present?

Answer 3

Pain and swelling in both hands/wrists/knees- stiffness in and around joints which is particularly bad in the morning is normal

Question 4

How does the stiffness in rheumatoid arthritis change with exercise?

Answer 4

It gets better

Question 5

Why do you need to that and modify the natural history of the disease?

Answer 5

The inflammation damages the joints (joint erosions on radiographs)

Question 6

What does extra-articular disease that can occur with rheumatoid arthritis consist of?

Answer 6

Rheumatoid nodules

Others are rare e.g. vasculitis, episcleritis- Rheumatoid factor forms immune complexes which can go anywhere

Question 7

Where can rheumatoid factor be detected?

Answer 7

In the blood

Question 8

Why is rheumatoid factor sometimes called rheumatoid antibody?

Answer 8

It is an IgM autoantibody against |gG

Question 9

What is the gender distribution of rheumatoid arthritis like?

Answer 9

More common in females- 3 times more

Question 10

What is the most common cause of cause?

Answer 10

Chronic synovitis

Question 11

What genetic component is very strongly linked to rheumatoid arthritis (shared epitope)?

Answer 11

A specific set of amino acids within the beta chain of the DR molecule which is conceived among all HLA subtypes associated with rheumatoid arthritis- referred to as the shared epitope

Question 12

What lifestyle factor increases susceptibility and severity of the disease?

Answer 12

Smoking

Question 13

What joints are most commonly affected in rheumatoid arthritis?

Answer 13

Metacarpophalangeal  joint
Proximal interphalangeal joint
Wrists
Knees
Ankles
Metatarsophalangeal joint

Question 14

What is the swan neck deformity?

Answer 14

Hyperextension at PIP

Hyperflexion at FIP

Question 15

What is boutonniere deformity?

Answer 15

Hyperflexion at PIP

Synovitis has damaged joints and the tendons are pulling an abnormal joint which causes “button deformity”

Question 16

What is dactylitis?

Answer 16

Whole digit is swollen

Question 17

If a patient presented with several fully swollen fingers how do you know this isn’t rheumatoid?

Answer 17

Not just the joints that are swollen

Question 18

What does tenosynovium do?

Answer 18

Wraps around tendons to allow them to move freely

Question 19

What are bursas?

Answer 19

Pockets of fluid that are found on the surface of the joints- can get inflamed causing bursitis

Question 20

What are subcutaneous nodules?

Answer 20

Rheumatoid factor produces immune complexes that can deposit in any tissue and they have a tendency to deposit in subcutaneous tissue and cause extra-articular manifestations

Question 21

Where are rheumatoid nodules commonly seen?

Answer 21

Along ulnar border of forearm

Question 22

What is rheumatoid factor?

Answer 22

IgM antibody that recognises and binds to Fc portion of |gG as their target antigen

Question 23

Why isn’t Fc portion of IgG used as diagnostic test?

Answer 23

1/3 of rheumatoid arthritis is rheumatoid factor negative

Question 24

Antibodies against what are highly specific for rheumatoid arthritis?

Answer 24

Citrullinated peptides

Question 25

What is citrullination of peptides mediated by?

Answer 25

Enzymes called peptidyl arginine deaminase (PADs)

Question 26

Why do citrullinated peptide antigens develop in rheumatoid arthritis?

Answer 26

PADs are present in high concentrations in neutrophils and monocytes and consequently there is increased citrullination of autologous peptides in inflamed synovium

Question 27

What extra-articular features are common in rheumatoid arthritis?

Answer 27

Fever Weight loss Subcutaneous nodules (Others are vasculitis, ocular inflammation, neuropathies, amyloidosis and lung disease)

Question 28

What are the three common extra-articular features caused by?

Answer 28

Abnormal cytokine response

Question 29

In the early stages, what radiographic abnormalities are there?

Answer 29

Juxta-articular osteopenia (less dense around joints)

Question 30

In later stages, what radiographic abnormalities are there?

Answer 30

Joint erosions at margins of joint | Joint deformity and destruction

Question 31

What happens to synovial membrane in rheumatoid arthritis?

Answer 31

It becomes thickened and chronically inflamed and will cause joint swelling

Question 32

What is pannus?

Answer 32

Synovial tissue that is chronically inflamed

Question 33

What happens after synovial tissue is inflamed?

Answer 33

It starts to eat away at adjacent bone starting with small area of bone which isn't covered by articular cartilage- periarticular erosions are seen first

Question 34

What is the cellular structure of synovium like?

Answer 34

It is almost a single cell lining and there are macrophages and fibroblasts (which produce synovial fluid) within synovial lining

Question 35

Why is synovial fluid viscous?

Answer 35

It contains a lot of hyaluronic acid

Question 36

What is articular cartilage made up of?

Answer 36

Type 2 collagen- main proteoglycan is aggrecan

Question 37

Why does the synovium become a proliferated mass of tissue (panes)?

Answer 37

Neovascularisation- formation of new blood vessels | Lymphangiogenesis- formation of new lymphatics

Question 38

What cells will there be a lot of within the joint?

Answer 38

``` Inflammatory: Activated B and T cells Plasma cells Mast cells Activated macrophages ```

Question 39

How is there a cytokine imbalance?

Answer 39

Excess of pro-inflammatory cytokines

Question 40

What are the key cytokines involved?

Answer 40

IL-1 IL-6 TNF-alpha

Question 41

What does pleiotropic mean?

Answer 41

When one gene influences two or more seemingly unrelated phenotypic traits. Consequently a mutation in a pleiotropic gene may have an effect on some or all traits simultaneously

Question 42

What is the aim of treatment for rheumatoid arthritis?

Answer 42

Prevent joint damage

Question 43

What are DMARDS?

Answer 43

Disease-modifying anti-rheumatic drugs | Dont cure but may induce remission and prevent joint damage- reduces inflammation in synovium

Question 44

What examples of DMARDs are there?

Answer 44

``` Methotrexate (commonly used) Sulphasalazine (commonly used) Hydroxychloroquine (commonly used) Leflunomide (uncommon) Gold (rarely used now) ```

Question 45

What is the problem with DMARDs?

Answer 45

All have significant adverse effects so require regular blood test monitoring during therapy

Question 46

What is the problem with biological therapy?

Answer 46

Drugs are very expensive | Increased infection

Question 47

What is TNF alpha inhibition associated with?

Answer 47

TNF alpha inhibition is associated with increased susceptibility to mycobacterial infection (in, particular, tuberculosis)- all patents need to be screened for TB

Question 48

What is B cell depletion therapy associated with?

Answer 48

Hepatitis B reactivation so need to screen all patients for hep B before treatment Also associated with JC virus infection and progressive multifocal leukoencephalopathy