Rheumatoid Arthritis

Question 1

what is rheumatoid arthritis?

what 3 things characterise it?

Answer 1

chronic inflammatory condition characterised by:
-PAIN
- STIFFNESS
- SYMMETRICAL SYNOVITIS
(inflammation of synovial membrane) of synovial joints.

Question 2

what are the key features of RA in terms of findings and presentation?

Answer 2

o Rheumatoid “factor” (Anti-IgG IgM-auto-antibody).
o Extra-articular disease
o Chronic arthritis.

Question 3

what are the features of chronic (rheumatoid) arthritis?

Answer 3

 Polyarthritis – swelling of small joints (hand/wrist).
 Symmetrical.
 Early morning stiffness.
 May lead to joint damage & destruction (swan neck and boutonniere deformity )

Question 4

which gender does RA affect most?

Answer 4

women (x3 more likely than men)

Question 5

what are the predispositions to RA?

Answer 5

• genetic component accounts for upto 60%

- environmental component like smoking contributes 25% of population-attributable risk

Question 6

what specific genetic component attributes to RA?

Answer 6

specific set of amino-acids in the beta-chain of the HLA-DR molecule

This specific set is then shared amongst all RA HLA sub-sets – termed “Shared epitope”.

Question 7

what joints are most commonly affected?

Answer 7

o	Metacarpophalangeal joints (MCP).
o	Proximal interphalangeal joints (PIP).
o	Wrists.
o	Knees.
o	Ankles.
o	Metatarsophalangeal joints (MTP).

Question 8

what are the deformities seen in RA?

Answer 8

o Symmetrical polyarthritis
– SYMMETRICAL!

o Swan-neck deformities
– affects ring-finger with hyper-extension of PIP joint and hyper-flexion of DIP joint.

o Boutonnière deformity – affects little finger with hyper-flexion of PIP joint.

Question 9

what are the primary sites of pathology in RA?

Answer 9

synovium located at:
o	Synovial joints
 – PIP joint synovitis.
o	Tenosynovium 
– extensor tenosynovitis (Tendons wrapped in Tenosynovium) 
o	Bursa
 – olecranon bursa

Question 10

what are subcutaneous nodules?

Answer 10

Made of a central area and peripheral area
c– fibrinoid necrosis surrounded by macrophages.
p– connective tissue

occur in about 30% of patients and associated with severe RA

Question 11

what is rheumatoid factor?

Answer 11

IgM antibodies against IgG i.e. anti-IgG antibodies

• IgG antibodies are the self-antigens that have been altered therefore RF has been created against them
• present in 70% at disease onset
• further 15% tested positive after 2 years of diagnosis

Question 12

what is the correlation with disease presentation and high RF?

Answer 12

o High RF proportionate with likelihood of joint damage.

o High RF proportionate with how ill the patient feels.

Question 13

what happens to citrullinated peptides in RA?

Answer 13

antibodies against citrullinated peptides are created

ACPA= anti-cyclic citrullinated peptide antibodies

• citrullination is a change that occurs to self-antigens induced by environment
• this is sampled by immune cells who take it T helper cells who cause B cell activation to produce antibodies

Question 14

how is citrullination of peptides done?

Answer 14

via peptidyl arginine deiminases (PADs)

arginine –> citrulline

PADs are more active at sites of inflammation when they are produced by neutrophils and monocytes.

Question 15

what lifestyle are ACPAs associated with?

Answer 15

ACPA is strongly associated with smoking (more citrullination in lungs) and HLA “Shared epitope”.

Question 16

what is the effect of having the shared epitope?

Answer 16

HLA-DR1, 4, 6, 10

epitope preferentially binds non-polar substances such as CITRULLINE

Question 17

what is the effect of smoking on citrulline?

Answer 17

enhance levels of citrulline

Question 18

what are the common extra-articular features of RA?

Answer 18

Pyrexia
weight loss.
SC nodules.

Question 19

what are the uncommon extra-articular features of RA?

Answer 19

	Vasculitis.
	Episcleritis – ocular inflammation.
	Neuropathies.
	Amyloidosis.
	Lung disease – fibrosis, nodules.
	Felty’s syndrome – (3) triad of – splenomegaly, leucopenia, RA.

Question 20

what are the early radiographic findings in RA?

Answer 20

Juxta-articular osteopenia (low bone density juxta-articular bone).

Question 21

what are the later radiographic findings in RA?

Answer 21

joint erosions at margins of joints.

Question 22

what are the even later radiographic findings in RA?

Answer 22

Joint deformity and destruction.

Question 23

what are the 3 things found in a synovial joint?

Answer 23

o Synovium
o Synovial fluid
o Articular cartilage

Question 24

what is the structure of synovium?

Answer 24

1-3 cells thin.

Contains – type-A synoviocyte (phagocytic), type-B synoviocytes (produce hyaluronic acid) and T1 collagen.

Question 25

what does synovial fluid contain?

Answer 25

Hyaluronic acid

GAG chains that are hydrophilic

Question 26

what type of collagen does articular cartilage contain?

Answer 26

Type 2 collagen.

Proteoglycan – mainly aggrecan.

Question 27

what substances are blockaded as part of biological therapy of RA?

Answer 27

pro-inflammatory cytokines:
TNF-a, IL-6 and IL-1

e.g. using infliximab, belumimab

Question 28

how can B-cells be depleted as part of biological therapy of RA? what drug is used?

Answer 28

RA by IV anti-CD20 antibodies

namely Rituximab

Question 29

what does the multidisciplinary approach to RA include?

Answer 29

physio, occupational therapy, hydrotherapy, surgery

Question 30

what type of drugs are used in RA treatment?

Answer 30

DMARDs – Disease-Modifying Anti-Rheumatic Drugs

Question 31

when should RA to treated?

Answer 31

as early as possible and aggressively to minimise joint destruction where inflammation happens over time

Question 32

what type of drugs are safer to use than steroids?

Answer 32

DMARDs (“steroid-sparing agents”) e.g methotrexate are safer and more effective in the long term

better than steroids as it won’t have the long term side effects of steroids

Question 33

what drug is used in glucocorticoid therapy of RA? how should usage be controlled?

Answer 33

prednisolone

avoid long term use due to its side effect but can be used short term to alleviate the symptoms

Question 34

what effect do DMARDs have on RA treatment?

Answer 34

induce remission (not cure) and prevent joint damage by reducing inflammation in synovium and slowing/preventing structural joint damage

slow effect

Question 35

example of DMARDs

Answer 35

methotrexate, sulphasalazine, hydroxychloroquine (commonly used)

Leflunomide, gold and penicillamine (rarely used).

regular blood monitoring needed due to significant side effects

Question 36

which antibody drugs can be used in RA management?

Answer 36

Rituximab & Infliximab:
chimeric antibodies (Fab mouse regions and human constant regions)

Adalimumab & Golimumab:
full human antibodies

used for severe RA

Question 37

when is biological therapy used?

Answer 37

when methotrexate (non-biological) has failed. Biological therapy involved all the antibody treatments (expensive and restricted) which is used later

Question 38

what is an increased risk with use of biological therapy?

Answer 38

increased risk of infection

Question 39

how can RA treatments lead to infection?

Answer 39

o TNF-a inhibition:
increased susceptibility to mycobacterial infections (screen patients for TB).
o B-cell depletion (can) lead to hepatitis B re-activation (so screen patients for Hep B).
o B-cell depletion (can) lead to JC virus infection and progressive multi-focal leukoencephalopathy (PML).

Question 40

examples of monoclonal antibody drugs?

Answer 40

belimumab
tocilizumab
denosumab

Question 41

what does the drug abatacept do?

Answer 41

blocks co-stimulation of T cells and therefore their activation

Question 42

what does the drug etanercept do?

Answer 42

inhibits TNF-alpha

Question 43

what are the key antibodies in rheumatoid ?

Answer 43

• rheumatoid factor

- anti- cyclic citrullinated peptide antibodies

Question 44

which HLA gene defect caused rheumatoid?

Answer 44

HLA DR4