RA

Question 1

What diseases are classified as Rheumatic Autoimmune?

Answer 1

Scleredema, SLE, RA, granulomatosis, Psoriatic disease, Sjorgens.

Question 2

What clinical features are common to all autoimmune rheumatic diseases? -5=

Answer 2

1. Malaise
2. Fatigue
3. Weight loss
4. Myalgia
5. Arthritis

Question 3

How is RA defined according to ACR/EULAR 2010?

Answer 3

The presence of synovitis in at least one joint, the absence of an alternative diagnosis better explaining the symptoms and a total score of at least 6 (of 10) from:

• 2-10 joints large = 1 point, 1-3 small joints = 2 points, 4-10 small joints = 3, >10 joints altogether = 5 points.
• RF or ACPA, low positive = 2 points, high positive = 3 points.
• at least a duration of 6 weeks = 1 point.

Question 4

How is RA defined according to BSR?

Answer 4

Persistent joint inflammation affecting at least three joint areas, involvement of the metacarpophalangeal (MCP=knuckles?) or metatarsophalangeal joints or early morning stiffness of at least 30 mins duration.

Question 5

What is the prevalence of RA?

Answer 5

3:1 in favour of females developing it.
0.81% of UK population. 1.16% of female population, 0.44% of male pop.
Increases with age until 75 then decreases.
Higher prevalence in colder areas of Europe.

Question 6

What factors can predispose to RA development? [3]

Answer 6

1. Genetic: HLA-DRB1
2. Environmental triggers: viral, bacterial, smoking, periodontitis.
3. Hormones or hormonal deficiency may promote development.

Question 7

What genetic factor can predispose RA development?

Answer 7

HLA-DRB1

Question 8

What environmental factors can predispose to RA development?

Answer 8

Viral infection
Bacterial infection
Smoking
Periodontitis

Question 9

What shared epitope is carried by the vast majority of RA patients?

Answer 9

HLA-DRB1

Question 10

What RA associated antibody is useful in diagnosing RA?

Answer 10

The Rheumatoid Factor (RF) which are antibodies to the Fc domain of IgG.

Question 11

What are the other RA specific antibodies? [3]

Answer 11

1. Anti-BiP
2. Anti-Sa
3. ACPA - anti-citrullinated protein antigen. (Fibrin etc)

Question 12

What are the typical signs and symptoms of RA? [5]

Answer 12

1. Disease onset is over weeks or months,
2. Painful, stiff joints due to inflammatory synovitis
3. Symmetrical swelling in small joints,
4. Large joints only sometimes affected.
5. Fatigue, flu-like symptoms, morning stiffness.

Question 13

What skin manifestations of RA can occur?

Answer 13

Rheumatoid nodules, ulcers, vasculitis.

Question 14

What CNS/PNS manifestations of RA can occur?

Answer 14

Cerebrovascular disease, mononeuritis multiplex as part of vasculitis, carpal tunnel syndrome.

Question 15

What eye manifestations of RA are there?

Answer 15

Scleritis, episcleritis, sicca syndrome.

Question 16

What assessment tools for RA exist? [6]

Answer 16

1. Sharp score (radiology)
2. Larsen index (radiology)
3. ACR response criteria
4. Eular
5. DAS
6. Health Assessment Questionnaire

Question 17

What radiological evidence of early RA may be present? [3]

Answer 17

1. soft tissue swelling, narrowing of joint space.
2. loss of cartilage, erosions.
3. Severe erosive damage to MTP joints of feet.

Question 18

What is the DAS28 score?

Answer 18

Numerical scale of 0-10 which indicated current activity of RA disease.

Question 19

What laboratory parameters would be evaluated when assessing a patient’s RA?

Answer 19

ESR, CRP, RF, FBC
Electrolytes, creatinine, hepatic enzyme levels.
Synovial fluid analysis.
Urinalysis.

Question 20

What is the general prognosis of RA?

Answer 20

Variable, if untreated = generally poor.
Aggressive nature of RA can lead to a rapid decline in the patient’s QOL. Increased risk of comorbidity compared with general population.

Question 21

What are the key indicators of a poor outcome in RA? [6]

Answer 21

1. Genetics: HLA-DRB1 genotype is associated with more severe form of RA.
2. Laboratory: High ESR or CRP level at outset. RF+ve, anti-CCP +ve.
3. Clinical assessment: many active joints, poor functional scores (HAQs)
4. Uneducated
5. Poor
6. Radiological lesions of early onset.

Question 22

What are the current management strategies for mild RA? (brief)

Answer 22

Analgesics as required.
NSAIDs +/- DMARDS.
Initial aggressive treatment with DMARDs and NSAIDS is the preferred treatment.

Question 23

What are the current management strategies for both moderate and severe RA? (brief)

Answer 23

Analgesics as required.
NSAIDS +/- DMARDS.
DMARDS +/- Biologics

Question 24

What current therapies are approved for symptomatic treatment of RA?

Answer 24

NSAIDS: such as ibuprofen, COX-2 inhibitors like celecoxib, normal analgesics like paracetamol.

Question 25

What type of drug is celecoxib?

Answer 25

COX-2 inhibitor, used in RA.

Question 26

Which drugs are used to prevent or impede joint damage and alleviate disease signs and symptoms?

Answer 26

1. Glucocorticoids 2. DMARDS: like methotrexate. 3. Biologics: like anti-TNFalpha, B cell therapy.

Question 27

Why are glucocorticoids used in RA treatment?

Answer 27

To prevent or impede joint damage and alleviate disease signs and symptoms. They are a class of anti-inflammatory corticosteroid (prednisolone) in oral or local injection.

Question 28

What effect does IL-6 release by mast cells in synovial joint have? [2]

Answer 28

1. Increased CRP levels. | 2. T and B cell stimulation.

Question 29

What is the effect of IL-1 release by mast cells? [3]

Answer 29

1. Increased recruitment of inflammatory cells. 2. Increased release of metalloproteases. 3. Increased osteoclast maturation and therefore bone destruction.

Question 30

Why does IL-1 release by mast cells lead to increased bone destruction?

Answer 30

IL-1 increases osteoclast maturation rate and therefore bone destruction.

Question 31

What causes mast cell activation?

Answer 31

Auto-antibody immune complex + Fc receptor.

Question 32

Why does Toclizumab cause a reduction in levels of CRP and B/T cell stimulation?

Answer 32

It blocks the IL-6 receptor and the IL-6 normally causes these effects.

Question 33

TNFalpha release by mast cells causes what? [5]

Answer 33

1. Increased expression of endothelial adhesion molecules 2. Increased T and B cell proliferation. 3. IL-1 and IL-6 production 4. Increased bone destruction. 5. Increased systemic and synovial inflammation.

Question 34

Why does TNFalpha release by mast cells cause increased bone destruction?

Answer 34

TNFalpha release -> increased IL-1 and IL-6 production. IL-1 increased osteoclast maturation rate. Osteoclasts are responsible for bone destruction.

Question 35

Name 5 common anti-TNFalpha agents:

Answer 35

1. Infliximab. 2. Etanercept. 3. Adalimumab. 4. Certolizumab. 5. Golimumab.

Question 36

What type of agent is infliximab?

Answer 36

Anti-TNFalpha. Murine + mouse.

Question 37

What is Anakinra?

Answer 37

An IL-1 inhibitor.

Question 38

How does Anakinra use lead to reduced bone destruction?

Answer 38

Anakinra is an IL-1 inhibitor. IL-1 causes: 1. Increased recruitment of inflammatory cells. 2. Increased release of metalloproteases. 3. Increased osteoclast maturation and therefore bone destruction.

Question 39

What type of agent is certolizumab peg?

Answer 39

Anti-TNFalpha agent, murine + human + PEG.

Question 40

What are the difference between the anti-TNFalpha agents licensed for RA?

Answer 40

``` Infliximab: murine and mouse. Etanercept: human Adalimumab: human Certolizumab: human + mouse + peg Golimumab: human. ```

Question 41

What type of agent is Etanercept?

Answer 41

Anti-TNFalpha. Human.

Question 42

What are the fully human anti-TNFalpha agents?

Answer 42

Etanercept. Adalimumab. Golimumab. Mouse + human: infliximab, Mouse + human + peg: Certolizumab.

Question 43

What is Rituximab?

Answer 43

B cell depleting monoclonal anti-CD20 antibody.

Question 44

What type of agent is Adalimumab?

Answer 44

Anti-TNFalpha. Human

Question 45

How does Rituximab cause B cell depletion?

Answer 45

It is a monoclonal anti-CD20 antibody which leads to Fc receptor gamma mediated antibody dependent cytotoxicity, complement-mediated cell lysis, growth arrest, B cell depletion.

Question 46

How does Abatacept function in RA treatment?

Answer 46

Soluble receptor composed of CTLA-4 and Fc fragment of IgG. Blocks interaction of CD90 and CD86 with CD28 on T cells. May also have an CD28 independent action to inhibit lymphocyte activation and cause T cell death.

Question 47

Abatacept blocks the interaction between [BLANK] and [BLANK] with CD28 on T cells.

Answer 47

Soluble receptor composed of CTLA-4 and Fc fragment of IgG. Blocks interaction of CD90 and CD86 with CD28 on T cells. May also have an CD28 independent action to inhibit lymphocyte activation and cause T cell death.

Question 48

What is abatacept?

Answer 48

Soluble receptor composed of CTLA-4 and Fc fragment of IgG. Blocks interaction of CD90 and CD86 with CD28 on T cells. May also have an CD28 independent action to inhibit lymphocyte activation and cause T cell death.

Question 49

Which RA treatment blocks an interaction between CD90 and CD86 with CD28 on T cells.

Answer 49

Abatacept is a soluble receptor composed of CTLA-4 and Fc fragment of IgG. Blocks interaction of CD90 and CD86 with CD28 on T cells. May also have an CD28 independent action to inhibit lymphocyte activation and cause T cell death.

Question 50

What is ACPA?

Answer 50

Highly specific antibody for RA. Can be found up to 14 years before the onset of the first symptoms. ACPA antibodies may present early in the disease and accurately predict the development of RA.