Immunosuppression and Rheumatology

Question 1

Outline the pathophysiology of RA

Answer 1

Autoimmune – T/B cells

Proinflam – IL1/6, TNF-alpha

Inflam change and proliferation of synovium = dissolution of cartilage and bone

Question 2

How do we diagnose 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

Question 3

Outline the treatment goals for RA

Answer 3

Early use of disease-modifying drugs

Aim to achieve good disease control

Use of adequate dosages

Use of combinations of drugs

Avoid long-term corticosteroids

Question 4

Outline the treatment goals for lupus

Answer 4

Symptomatic relief e.g arthralgia, Raynaud’s phenomenon

Reduction in mortality

Prevention of organ damage

Reduction in long term morbidity caused by disease and by drugs

Question 5

Describe the mechanism of action of systemic corticosteroids

Answer 5

prevent interleukin (IL)–1 and IL-6 production by macrophages

inhibit all stages of T-cell activation

Question 6

Discuss the use of azathioprine

Answer 6

Maintenance therapy = SLE and vasculitis

Metabolised by enzyme TPMP (important the levels are checked)

Decreases DNA/RNA synthesis

Question 7

What are the possible side effects of azathioprine?

Answer 7

Bone marrow suppression = monitor FBCs

Increased risk of malignancy

Increased risk of infection

Question 8

Discuss calcineurin inhibitors (ciclosporin and tacrolimus)

Answer 8

Used in transplantation, atopic dermatitis and psoriasis

Active against T helper cells

Check BP and eGFR regularly – renal toxicity

Question 9

Discuss the use of mycophenolate mofetil

Answer 9

Used in transplantation

Maintenance therapy for lupus

Inhibits guanosine synthesis

Impairs B/T cell prolif

Question 10

What are the common side effects from mycophenolate mofetil?

Answer 10

Nausea, vomiting, diarrhoea

Myelosupression

Question 11

Outline the use of cyclophosphamide

Answer 11

CYTOTOXIC = metabolite acrolein, give aggressive hydration to flush out the kidneys

Treats lymphoma, leukaemia, lupus nephritis

Alkylating agent -cross links DNA so that it cannot replicate

Suppresses T/B cell activity

Question 12

Discuss methotrexate

Answer 12

Gold standard for RA

Blocks DNA synthesis, inhib T cell activation, suppression of intercellular adhesion molecule expression by T cells

Administered = PO, IM, S/C

Given once a week due to toxicity

Question 13

What are the ADRs regarding methotrexate?

Answer 13

Mucositis

Marrow suppression

Serious = hepatitis, cirrhosis, pneumonitis

Highly teratogenic

Question 14

Discus sulphalazine

Answer 14

Treats RA

Inhibits T cell proliferation

Reduces neutrophil chemotaxis and degranulation

Not carcinogenic - safe in pregnancy

Question 15

Outline the side effects of sulfasalazine

Answer 15

myelosuppression

hepatitis

rash

Nausea, vomiting, abdo pain

Question 16

Briefly outline the newer ‘biologicals’ and their range of indications

Answer 16

Monoclonal Ab

Control inflam, asthma, IBD, myeloma, RA

Question 17

Outline the action of drugs that block TNF α

Answer 17

Block the release of TNF-alpha = stops a pro-inflam cytokine

= decreases inflam, angiogenesis, joint destruction

Screen for latent TB

Rituximab = binds CD20 on B cells causing apoptosis (effective in RA)