Lupus

Question 1

Systemic lupus erythematosus?

Answer 1

Autoimmune disease involving innate and adaptive immune system disturbance
Has autoantibodies - antibodies to nuclear components
Antibody-antigen (immune complexes) -> chronic tissue inflammation (particularly joints, skin and kidney)

Question 2

SLE rash example?

Answer 2

Malar rash

Question 3

Autoimmune connective tissue disorder? General points

Answer 3

1. Arthralgia and arthritis typically non-erosive (unlike RA)
2. Serum autoantibodies characteristic
3. Raynaud’s phenomenon common

Question 4

Raynaud’s phenomenon?

Answer 4

Intermittent vasospasm of digits, usually triggered by cold exposure
Triphasic colour changes

Question 5

Typical Raynaud’s colours?

Answer 5

White - vasospasm leading to blanching of digit
Blue - cyanosis as static venous blood deoxygenates
Red - reactive hyperaemia

Severe Raynaud’s - tissue ischaemia, ulcers and necrosis

Question 6

SLE epidemiology?

Answer 6

15-45
F:M - 9:1
Africa > Asian > white European

Question 7

Clinical features? Skin

Answer 7

Malar rash - erythema that spares nasolabial fold
Photosensitive rash
Mouth ulcers
Hair loss

Question 8

Clinical features? Vascular

Answer 8

Raynaud’s

Question 9

Clinical features? MSK

Answer 9

Arthralgia and arthritis (non-erosive)

Question 10

Clinical features? Internal organs

Answer 10

Serositis (pericarditis, pleuritis, rarely peritonitis)
Renal disease - glomerulonephritis
Cerebral disease
Myocarditis

Question 11

Clinical features? Haematological

Answer 11

Autoimmune thrombocytopenia
Haemolytic anaemia
Lymphopenia

Question 12

Clinical features? Other

Answer 12

Lymphadenopathy
Fever in absence of infection

Question 13

Anti-nuclear antibodies?

Answer 13

Hallmark of SLE, in all patients
Examples of other autoantibodies:
Anti-ds-DNA antibody
Anti-Ro
Anti-La
Anti-Smith
Anti-RNP

Question 14

Anti-phospholipid antibodies?

Answer 14

Directed to phospholipids on cell membrane
Associated with increased risk of thrombosis and pregnancy loss

persistent APL + clinical event = anti-phospholipid antibody syndrome

Question 15

Main autoantibodies in SLE?

Answer 15

Antinuclear antibodies - in all SLE, non-specific

Anti-double stranded DNA antibodies - specific for SLE, serum level DO correlate with disease activity

Anti-phospholipid antibodies - can occur in absence of SLE (primary anti-phospholipid antibody syndrome)

Anti-Sm antibodies - specific for SLE, serum levels DON’T correlate with disease activity

Question 16

SLE immunopathogenesis?

Answer 16

Overactivity of type 1 interferon pathway
Complement pathway abnormalities
Overactive B and T cells

Question 17

Waste disposal hypothesis

Answer 17

1. Apoptosis -> translocation of nuclear antigens to membrane surface
2. Impaired clearance of apoptotic cells = enhanced presentation of nuclear antigens to immune cells
3. B cell autoimmunity
4. Tissue damage by antibody effector mechanisms

Question 18

SLE investigations? Inflammation

Answer 18

High ESR, usually normal CRP

Question 19

SLE investigations? Renal

Answer 19

Measure urine protein, creatinine, albumin
Kidney biopsy if persistent proteinuria

Question 20

SLE investigations? Immunological

Answer 20

ANA
Anti-ds-DNA antibodies
Complement consumption (low C3 + C4)
Antiphospholipid antibodies

Question 21

SLE complement and antibodies in unwell patient?

Answer 21

Low C3 + C4
High anti-dsDNA antibodies

Question 22

SLE management aims?

Answer 22

1. Treat SLE and prevent flares
2. Prevent ionotropic harm of steroids (infection, osteoporosis, avascular necrosis)
3. Specific treatment

Question 23

SLE management? Pharmacology

Answer 23

Hydroxychloroquine recommended for all lupus patients
steroids for flare
Serious disease - immunomodulatory (mycophenolate, methotrexate, Azathioprine)

Question 24

SLE renal disease treatment?

Answer 24

Mycophenolate +/- rituximab

Question 25

Severe or life threatening SLE treatment?

Answer 25

IV steroids + IV cyclophosphamide

Question 26

SLE + antiphospholipid antibody syndrome treatment?

Answer 26

Anticoag (warfarin)

Question 27

SLE and pregnancy considerations?

Answer 27

1. Antiphospholipid antibodies associated with miscarriage (give aspirin or heparin) 2. Pregnancy increased Haemodynamic demands so will worsen renal dysfunction 3. Ro antibodies - can cause fetal heartblock 4. Drugs

Question 28

Drug considerations? SLE and pregnancy, unsafe and safe

Answer 28

Unsafe - MMF, cyclophosphamide, methotrexate and warfarin are teratogenic Safe - Hydroxychloroquine, Azathioprine and low weight molecular heparin

Question 29

Ionotopic steroid side effects?

Answer 29

Infection, osteoporosis, avascular necrosis