Rheumatology & Immunosuppression

Question 1

What is rheumatoid arthritis?

Answer 1

An autoimmune, multisystems disease which is initially localised to the synovium
Involves destruction of cartilage and bone

Question 2

What key features do we look for when diagnosing RA?

Answer 2

Morning stiffness >1 hour 
Arthritis of >3 joints 
Arthritis of hand joints 
Symmetrical arthritis 
Rheumatoid nodules 
Serum rheumatoid factor 
X-ray changes (LOSS)

Question 3

What are the treatment goals for RA?

Answer 3

Symptomatic relief
+
Prevention of joint destruction

Question 4

Give some examples of immunosuppressant drugs

Answer 4

Corticosteroids 
Azathrioprine 
Ciclosporin 
Tacrolimus 
Mycophenolate mofetil

Question 5

What is the mechanism of action of corticosteroids?

Answer 5

Prevent IL-1 and IL-6 production by macrophages which inhibits all stages of T cell activation

Question 6

What is the gold standard treatment for RA?

Answer 6

Methotrexate

Question 7

Apart from for RA, what might Methotrexate be used to treat?

Answer 7

Malignancy
Psoriasis
Crohn’s disease

Question 8

Methotrexate has a very similar chemical structure to what?

Answer 8

Folic acid

Question 9

What is the mechanism of action of Methotrexate?

Answer 9

Competitive, reversible inhibition of dihydrofolate reductase (DHFR)
Inhibits the synthesis of DNA, RNA and proteins

Question 10

How does Methotrexate target rapidly dividing cells specifically (i.e. cancer cells)?

Answer 10

It is cytotoxic during S-phase of the cell cycle

Question 11

How does Methotrexate aid in the treatment of RA?

Answer 11

Mechanism is not clear

Possibly inhibits T cell activation

Question 12

How can Methotrexate be administered?

Answer 12

Orally, Intramuscularly, Subcut

Question 13

What is the dosing of Methotrexate?

Answer 13

WEEKLY dosing

Has a very long half life

Question 14

Name some adverse effects of Methotrexate

How can these be avoided?

Answer 14

Mucositis
Marrow suppression
Highly teratogenic and may cause abortion

Folic acid supplementation
Avoid in pregnancy

Question 15

What are the immunological effects of Sulfasalazine?

Answer 15

T cell inhibition, possible apoptosis, inhibition of IL-2

Neutrophil reduced chemotaxis and degranulation

Question 16

Sulfasalazine is useful in the treatment of what condition?

Why?

Answer 16

IBD

It is poorly absorbed and has its main activity within the intestine

Question 17

Name some adverse effects of sulfasalazine

Answer 17

Myelosupression 
Hepatitis 
Rash 
Nausea 
Vomiting 
Abdo pain

Question 18

What conditions might Azathioprine be useful to treat?

Answer 18

Maintenance of SLE and vasculitis

Question 19

What should be tested before prescribing Azathioprine?

Answer 19

TPMT activity- it is responsible for the cleavage of Azathioprine into its active form and is highly polymorphic

Question 20

What is the mechanism of action of Azathioprine?

Answer 20

It is a pro drug that is cleaved by TPMT into 6-MP which decreases DNA and RNA synthesis

Question 21

List some adverse effects of Azathioprine

Answer 21

Bone marrow suppression:
Increased risk of malignancy
Increased risk of infection
Hepatitis

Question 22

What is Mycophenolic (mofetil) acid used for in practice?

Answer 22

To avoid transplant rejection

For lupus nephritis

Question 23

What are the most common side effects of Mycophenolic (mofetil) acid?

Answer 23

Nausea
Vomiting
Diarrhoea
Myelosuppression

Question 24

What is Mycophenolic acids mode of action?

Answer 24

Impairs B and T cell proliferation whilst sparing other rapidly dividing cells

Question 25

Name a cyclotoxic agent that is a prodrug with indications in lymphoma, leukaemia and solid cancers as well as lupus nephritis

Answer 25

Cyclophosphamide

Question 26

List some important considerations when using cyclophosphamide and how these can be overcome in practice

Answer 26

Bladder malignancy- +++++ hydration +/or Mensa Infertility- care when giving to young patients Dose should be adjusted in patients with renal impairment

Question 27

Which drug is safer as just as effective as cyclophosphamide in the treatment of lupus nephritis?

Answer 27

Mycopenolate mofetil

Question 28

List some monoclonal antibodies that may be used in the treatment of rheumatoid conditions such as RA, Crohn's and psoriasis

Answer 28

Rituximab - RA, SLE, vasculitis Adalimumab - RA, AS, psoriasis, Crohn's Golimumab - RA, AS, UC

Question 29

How do monoclonal antibodies that block TNFalpha work work?

Answer 29

They reduce inflammation by blocking the cytokine cascade They reduce angiogenesis They reduce joint destruction

Question 30

What must you screen for before stating a patient on Anti-TNFalpha therapy? + How?

Answer 30

Latent TB | Quantiferon gold

Question 31

How does Rituximab work to reduce autoimmune responses in patients with rheumatological conditions?

Answer 31

It binds to CD20 on a specific B cell subset and causes apoptosis

Question 32

What do you need to keep a close eye on in patients that are taking calcineurin inhibitors?

Answer 32

BP and eGFR | Due to renal toxicity

Question 33

What is the mode of action of calcineurin inhibitors? | Give some examples

Answer 33

Activity against T cells, preventing production of IL-2 | Ciclosporin and tacrolimus