7. Systemic lupus erythematosus

Question 1

What gender and ethnicities does SLE mainly affect?

Answer 1

• Females

* Afro-caribbeans, Asians and Chinese

Question 2

What does SLE predominantly affect?

Answer 2

Joints and skin

Question 3

What main symptoms do mild SLE disease patients have?

Answer 3

Rash and arthritis

Question 4

Which genes may impact SLE pathogenesis?

Answer 4

Fc receptors, IRF5, CTLA4, MHC class II

Question 5

How does SLE present?

Answer 5

• Can be vague initially
• Malaise, fatigue, fever, weight loss
• Lymphadenopathy

Question 6

What are the specific (and other non-specific) features of SLE?

Answer 6

• Butterfly rash (malar rash)
• Alopecia
• Arthralgia
• Raynaud’s phenomenon

(other non-specific:
• Inflammation of the kidney, CNS, heart and lungs
• Accelerated atherosclerosis
• Vasculitis)

Question 7

List the criteria that a patient must have at least 4/11 of, for the diagnosis to point towards lupus?

Answer 7

• S - serositis (pleuritis or pericarditis)
• O - oral ulcers
• A - arthritis
• P - Photosensitivity
• B - blood (haematological) disorder
• R - renal disorder (proteinuria)
• A - antinuclear antibody raised in titre
• I - immunological disorder (anti-dsDNA)
• N - neurological disorder
• M - malar rash
• D - discoid rash

SOAP BRAIN MD

Question 8

What does it mean by the fact that the erythematous rash is ‘non-pruritic’?

Answer 8

Doesn’t itch

Question 9

When is the erythematous rash damaging?

Answer 9

If it extends from the epidermis into the dermis - leads to de-pigmentation and scarring

Question 10

Where is the malar rash mainly seen?

Answer 10

On the cheeks and bridges of the nose

Question 11

What triggers SLE?

Answer 11

• Genetic predisposition - not enough on it’s own
• Environmental trigger e.g. EBV - not enough on it’s own
• You need innate immune hyper-activation (hyperactive B cells), so that antibody production over-responds to the combination of the genetic and environmental effects

Question 12

How do hyperactive B cells lead to the symptoms of SLE?

Answer 12

• Produce autoantibodies
• Further immune activation (cycle)
• Immune complexes generated for systemic deposition
• Leads to intense complement-mediated inflammation and organ damage (e.g. in skin and kidneys)

Question 13

How does the abnormal clearance of apoptotic cells lead to complement activation?

Answer 13

=> dendritic cell uptake of autoantigens and activation of B cells
=> B cell Ig class switching, affinity maturation
=> IgG autoantibodies
=> immune complexes
=> complement activation

Question 14

What is the differential diagnosis for SLE?

Answer 14

• ANA (anti-nuclear antibody) positive - immunofluorescence
• Other autoimmune connective tissue disease
• Cutaneous lupus
• Drug induced lupus - symptoms will stop after cessation of drug e.g. hydrazine

Question 15

What type of staining are you more likely to see in SLE and systemic sclerosis?

Answer 15

• SLE - homogenous nuclear staining

* Systemic sclerosis - nucleolar pattern

Question 16

What specific anti-nuclear antibodies point towards SLE?

Answer 16

• Anti-dsDNA antibodies and Sm
• Anti-Sm antibodies
• Anti-Ro and/or La antibodies

Question 17

Which anti-nuclear antibodies can cross the placenta and what affect does this have?

Answer 17

• Anti-Ro

* Cause heart block in the foetus

Question 18

What 3 lab test show the patient has active lupus?

Answer 18

• High titre ANA
• Hight titre anti-dsDNA antibody
• Low C3/C4

Question 19

Describe the haematological features in SLE

Answer 19

• Lymphopaenia - low lymphocyte count
• Anaemia (autoimmune haemolytic)
• May have leukopenia and thrombocytopenia - life threatening

Question 20

Describe the renal features of SLE

Answer 20

• Proteinuria and haematuria
• Absence of infection in conjunction with these are indicative of nephritis
• Active urinary sediment

Question 21

What do SLE patients generate more apoptotic cells on the skin in response to?

Answer 21

UV light

Question 22

What 3 groups can SLE be divided in?

Answer 22

• Mild - joint +/- skin involvement
• Moderate - inflammation of other organs
• Severe - severe inflammation of vital organs

Question 23

How do you treat mild SLE?

Answer 23

• Paracetamol or NSAIDs
• Monitor kidney function
• Hydroxychloroquine if athropathy gets worse
• Topical corticosteroid for rash

Question 24

How do you treat moderate SLE?

Answer 24

• Corticosteroids - start high initial dose

* Then give IV methylprednisolone

Question 25

How do you treat severe SLE?

Answer 25

• Azathioprine - immunomodulatory therapy (steroid-sparing)

* Cyclophosphamide

Question 26

Give and describe examples of novel treatment of sever SLE

Answer 26

Mycophenolate mofetil
• as effective as cyclophosphamide
• doesn’t risk infertility (but is teratogenic)
• reversible inhibitor of inosine monophosphate dehydrogenase (rate-limiting enzyme in de novo purine synthesis, which lymphocytes are dependent upon)

Rituximab
• anti-CD20

Question 27

What is the survival of SLE patients without and with nephritis?

Answer 27

• Without nephritis - 85% 15 year survival

* With nephritis - 60% 15 year survival

Question 28

Is disease more aggressive in males or females?

Answer 28

Males