Systemic Lupus Erythematosus

Question 1

List 5 diseases that come under the category of ‘connective tissue disease’

Answer 1

Rheumatoid arthritis
SLE  
Systemic sclerosis  
Dermatomyositis/ polymyositis  
Sjogren’s syndrome

Question 2

Which gender does SLE more commonly affect?

Answer 2

Females 9:1

Question 3

Describe the presentation of SLE including 4 specific features.

Answer 3

Malaise, fatigue, weight loss, fever, lymphadenopathy  
Specific features:  
Butterfly rash
Alopecia  
Arthralgia  
Raynaud’s phenomenon

Question 4

Describe the characteristics of the rash seen in SLE.

Answer 4

Tends to go across the nose
May look like acne
Not painful or itchy

Question 5

Describe the pathogenesis of SLE.

Answer 5

SLE patients have a defect in apoptosis
Apoptotic cells are not cleared properly so persist + expose their nuclear antigens + autoantibodies are generated against these nuclear antigens
The defect in apoptosis is combined with B cell hyperactivity
Overactive B cells are exposed to the nuclear antigens + plasma cells start to produce autoantibodies that circulate + form immune complexes
Immune complexes deposit in tissues + activate complement leading to inflammation

Question 6

What is the first investigation performed in the diagnosis of SLE?

Answer 6

Check for anti-nuclear antibodies

not specific for SLE though

Question 7

What is the pattern of antinuclear antibodies binding to nuclear antigens in SLE?

Answer 7

Homogenous

Antibodies to DNA

Question 8

What conditions are associated with the presence of anti-Ro and anti-La antibodies? (other than SLE)

Answer 8

Neonatal lupus syndrome
Sjogrens syndrome
Subacute cutaneous lupus erythematosus

Question 9

What are the biological features seen in SLE? (e.g. in serum)

Answer 9

Increased complement consumption
Anti-cardiolipin antibodies
Lupus anticoagulant
Beta 1 glycoprotein

Question 10

Describe the haematological features of SLE.

Answer 10

SLE generally associated with low blood counts  
Lymphocytopenia  
Normochromic anaemia 
Leukopaenia
Thrombocytopenia  
Autoimmune haemolytic anaemia

Question 11

What renal changes might occur in SLE?

Answer 11

Proteinuria
Haematuria
Active urinary sediment

Question 12

List 4 clinical features that could help pre-empt severe attacks in SLE.

Answer 12

Malaise
Weight loss
Alopecia
Rash

Question 13

List 3 laboratory markers that could help pre-empt severe attacks in SLE.

Answer 13

Raised ESR
Raised anti-dsDNA antibodies
Increased complement consumption

Question 14

Describe the differences between mild, moderate and severe disease in SLE.

Answer 14

Mild: skin + joint involvement
Moderate: inflammation of other organs (e.g. pleuritis, pericarditis)
Severe: severe inflammation of vital organs

Question 15

Describe the treatment of mild disease.

Answer 15

Paracetamol + NSAIDs
Hydroxychloroquine (for arthropathy + cutaneous manifestations)
Topical corticosteroids

Question 16

Describe the treatment of moderate disease.

Answer 16

Corticosteroids

Start with a HIGH dose + titre downwards

Question 17

Describe the treatment of severe disease.

Answer 17

Azathioprine: effective steroid-sparing drug, safe in pregnancy
Risk of neutropenia/ BM suppression so needs regular blood monitoring
Cyclophosphamide: used if there is severe organ involvement
Causes BM suppression, infertility, cystitis

Question 18

What are the following drugs used for and what is their mechanism of action:
Mycophenolate mofetil
Rituximab

Answer 18

Treatment for severe SLE
MM: Immunosuppressive
R: Anti-CD20 antibody, causes depletion of B cells

Question 19

SLE has and early peak and a late peak in mortality. What are the usual causes of the two peaks?

Answer 19

Early`: renal failure, CNS disease, infection

Late: MI + stroke

Question 20

What can usually be seen on the blood film of a patient with SLE?

Answer 20

Schistocytes 
Spherocytes
Anisocytosis
Poikilocytosis
Fibrin strands
Thrombocytopaenia  
Few leukocytes

Question 21

Describe the appearance of a renal biopsy in a patient with SLE

Answer 21

Proliferative

Crescentic glomerulonephritis

Question 22

What is principally effected in SLE? What is sometimes also effected?

Answer 22

Joints + Skin

Lungs, Kidneys + Haematology

Question 23

What genetic deficiencies are associated with SLE?

Answer 23

Complement deficiency C1q + C3

Question 24

List 4 severe features which may be present in undiagnosed SLE

Answer 24

Psychosis
Renal failure
Accelerated atherosclerosis
Vasculitis

Question 25

What causes onset of SLE?

Answer 25

Genetic predisposition + Environmental triggers (e.g. virus)
Leads to chronically activated innate immune system,
drives a switch to adaptive immune response, B cell hyperactivity, generation of autoantibodies + immune complexes

Question 26

What antibodies are seen in the majority of SLE patients?

Answer 26

Anti-dsDNA

Question 27

What antibodies are seen in ~ 20% of SLE patients, highly specific for lupus?

Answer 27

Anti Sm antibodies

Question 28

What is the unusual laboratory marker seen in SLE?

Answer 28

CRP stays normal in active disease