Lupus

Question 1

What are the autoimmune connective tissue disorders?

Answer 1

• systemic lupus erythmatosus
• autoimmue inflammatory muscle disease
• systemic sclerosis (scleroderma)
• Sjorgen’s syndrome

Question 2

When are overlap syndromes of autoimmune connective tissue disorders most likely to occur?

Answer 2

In childhood

Question 3

What is SLE?

Answer 3

• autoimmune disorder affecting both innate and adaptive immune systems
• involves autoantibodies to nuclear components of cells
• immune complexes and other mechanisms cause chronic tissue inflammation

Question 4

Where is inflammation most likely to manifest in SLE?

Answer 4

Joints, skin and kidney

Question 5

How is arthirits and artharlagia different in SLE than in RA?

Answer 5

Non-erosive

Question 6

What is a common feature of autoimmune connective tissue disorders?

Answer 6

Raynaud’s phenomenon

Question 7

What is Raynaud’s phenomenon?

Answer 7

• intermittent vasospasm of digits
• usually triggered by cold exposure

Question 8

What is the triphasic colour change which happens in Raynaud’s phenomenon?

Answer 8

1. White - vasospasm causes digits to blanch
2. Blue - cyanosis due to static venous blood becoming deoxygenated
3. Red - reactive hyperaemia

Question 9

What are the features of severe Raynaud’s?

Answer 9

Tissue ischaemia, ulcers and necrosis

Question 10

What are the common clinical features of SLE?

Answer 10

• malar (butterfly) rash
• photosensitive rash
• mouth ulcers
• hair loss
• Raynaud’s
• arthralgia
• serositis
• renal disease
• cerebral disease
• myocarditis
• autoimmune thrombocytopenia
• haemolytic anaemia
• lymphopenia
• lymhodenopathy
• fever with no infection

Question 11

What is the hallmark feature of SLE?

Answer 11

• Anti-nuclear antibodies (ANA)
• found in all SLE patients

Question 12

Why can ANA be used to rule out lupus but not diagnose it?

Answer 12

ANA is not specific for lupus and can be seen in other diseases, infections and even in healthy people

Question 13

What will the clinical laboratory report if ANA is positive?

Answer 13

• strength (maxiumum dilution at which antibody can still be detected)
• pattern of staining (suggests which autoantigen the antibodies are reacting to)

Question 14

Which further tests indicate that a patient is positive for SLE?

Answer 14

• anti-ds-DNA antibodies
• anti-Ro
• anti-La
• anti-Smith
• anti-RNP

Question 15

Which other antibodies do some patients with SLE present with?

Answer 15

Antiphospholipid antibodies (APL)

Question 16

What is the presence of APL associated with?

Answer 16

• arterial thrombosis (stroke)
• venous thrombosis (DVT)
• pregnancy loss

Question 17

What is anti-phospholipid antibody syndrome?

Answer 17

• presistent presence of APL + clinical event
• cann occur in absence of SLE (primary APL syndrome)

Question 18

Which antibodies are specific for SLE?

Answer 18

• anti-double stranded DNA antibodies
• anti-Smith antibodies

Question 19

Which antibody specific to SLE has serum levels which indicate the severity of the diesease?

Answer 19

Anti-ds DNA antibodies

Question 20

What is the immunopathogenesis of SLE?

Answer 20

1. Interference with innate immunity
   - overactivity of type 1 interferon pathway
   - complement pathway abnormalities
2. Interference with adaptive immunity
   - autoreactive B and T cells

Question 21

How does the immune system generate a repsone to nuclear antigens?

Answer 21

Waste disposal hypothesis

Question 22

What is the waste disposal hypothesis?

Answer 22

• apoptosis translocates nuclear antigens to the membrane surface
• impaired clearance of apoptotic cells means more nuclear antibodies are presented to immune cells
• causes B cell autoimmunity
• leads to tissue damage by antibodies activating complement and Fc receptor engagement

Question 23

Why are the manifestations of SLE so varied?

Answer 23

Autoimmunity is systemic so almost any organ can be involved

Question 24

Which investigations are done for SLE?

Answer 24

• ESR (high)
• CRP (usually normal)
• FBC (anaemia, lymphopenia, thrombocytopenia)
• urinalysis to measure urine protein
• creatinine
• U&E
• albumin
• kidney biopsy is persistent proteinuria
• ANA
• anti-ds DNA
• compelement (low C3 and C4)
• ALP

Question 25

Delete

Question 26

What should be measured in patients who are on medication for SLE and why?

Answer 26

- FBC and LFT - may have adverse reactions to the medication

Question 27

How do you measure disease activity in SLE?

Answer 27

- clinical symptoms and signs - low C3 and C4 levels - high anti-ds DNA antibodies

Question 28

What are the general principals of managing SLE?

Answer 28

- aim for remission or low disease activity and preventing flare ups - balance controlling disease with avoiding iatrogenic harm from steroids - choose treatment depending on the disease severity and organ manifestations

Question 29

What are the steroid side effects seen in SLE?

Answer 29

- infection - osteoporosis - avascular necrosis (necrosis of bone, often affecting hips) especially in patients with ALP

Question 30

Which medications are recommended for all patients with SLE?

Answer 30

Hydroxychloroquine

Question 31

When can steroids be used for SLE?

Answer 31

In acute flare ups

Question 32

What medications are used in more serious SLE?

Answer 32

Immunomodulatory agents (mycophenolate, methotrexate, azithioprine)

Question 33

Which medications are used for kindey disease in SLE?

Answer 33

Mycophenolate +/- rituximab

Question 34

Which medications are used in persistently active SLE?

Answer 34

- B cell targeted therapies - rituximab (depeltes B cells, anti-CD20) - belimumab (anti-BAFF, cytokine needed for B cell survival)

Question 35

How do you treat life-threatening disease e.g myocarditis?

Answer 35

- IV steroids - IV cyclophosphamide - +/- rituximab

Question 36

What should patients with SLE and antiphospholipid antibody syndrome be given?

Answer 36

Warfarin for anticoagulation

Question 37

What are the emerging therapies for SLE?

Answer 37

Interferon receptor blockade e.g anifrolumab

Question 38

Who does SLE usually affect?

Answer 38

Women during their reproductive years

Question 39

What needs to be taken into consideration when treating patients with SLE who are of child bearing age?

Answer 39

- risk of disease and drugs to both mother and fetus - better outcomes with pre-pregnancy planning and getting SLE into remission first

Question 40

What is the effect of ALP on pregnancy?

Answer 40

- associated with miscarriage - can reduce risk with aspirin or heparin

Question 41

How does pregnancy affect renal function?

Answer 41

Increases haemodynamic demands which worsens renal function

Question 42

What can Ro antibodies cause in pregnancy?

Answer 42

Fetal heartblock

Question 43

Which medications for SLE are teratogenic?

Answer 43

- MMF - cyclophosphamide - methotrexate - warfarin

Question 44

Which medication for SLE are safe for pregnancy?

Answer 44

- hydroxychloroquine - azathioprine - low molecular weight heparin