Systemic Lupus Erythematosus

Question 1

What diseases come under the category of ‘connective tissue disease’?

Answer 1

SLE  
Systemic sclerosis  
Dermatomyositis/polymyositis  
Sjogren’s syndrome  
Mixed connective tissue disease

Question 2

Which gender does SLE more commonly affect?

Answer 2

Females 10:1

Question 3

Describe the presentation of SLE including some specific features.

Answer 3

Malaise, fatigue, weight loss, fever, lymphadenopathy

Specific features:  
Butterfly rash
Alopecia  
Arthralgia (pain in a joint.)
Long history of Raynaud’s phenomenon

Question 4

Describe the characteristics of the rash seen in SLE.

Answer 4

It tends to go across the nose
It may look a bit like acne
It is not painful or itchy
Some rashes become depigmented when the inflammation spreads to the dermis (depigmentation and scarring is irreversible)

Question 5

Describe the pathogenesis of SLE.

Answer 5

SLE patients have a defect in apoptosis

1. abnormal clearance of apoptotic cell material
   so they persist and expose their nuclear antigens
2. autoantibodies are generated, dendritic cell uptake of autoantigens and activation of B cells
3. The defect in apoptosis is combined with B cell hyperactivity
4. overactive B cells are exposed to the nuclear antigens and the plasma cells begin to produce autoantibodies that circulate and form immune complexes
5. The immune complexes deposit in tissues and 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 (this is not diagnostic/specific for SLE though)

Question 7

The pattern with which the antinuclear antibodies bind to the nuclear antigens is important in reaching a diagnosis. List some different patterns and the antigens they are associated with.

Answer 7

1. Homogenous – ABs to DNA
2. Speckled – ABs to Ro, La, Sm and RNP
3. Nucleolar – topoisomerase – scleroderma
4. Centromere – limited cutaneous scleroderma

Question 8

What conditions are associated with the presence of anti-Ro and/or anti-La antibodies?

Answer 8

Neonatal lupus syndrome

Subacute cutaneous lupus erythematosus

Question 9

What are some other tests that can be done for SLE?

Answer 9

Measuring complement levels
Anti-cardiolipin antibodies
Lupus anticoagulant
Beta 1 glycoprotein

Question 10

Describe the haematological features of SLE.

Answer 10

SLE is generally associated with low blood counts

Thrombocytopenia
Lymphopenia
Normocytic anaemia
Autoimmune haemolytic anaemia

Question 11

What renal changes might occur in SLE?

Answer 11

Proteinuria
Haematuria
Active urinary sediment

Question 12

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

Answer 12

Malaise, weight loss, alopecia, rash

Question 13

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

Answer 13

Raised ESR
Raised anti-dsDNA antibodies
Reduced complement levels

Question 14

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

Answer 14

Mild – skin and 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 and NSAIDs
Hydroxychloroquine (good for arthropathy and cutaneous manifestations)
Topical corticosteroids

Question 16

Describe the treatment of moderate disease.

Answer 16

ORAL GLUCORTICOIDS
Start with a HIGH dose and titre downwards
(high dose toxic so give w steroid sparing agent to lower dose needed)

Question 17

Describe the treatment of severe disease.

Answer 17

Azathioprine – useful steroid-sparing drug
Has a risk of neutropenia/bone marrow suppression so needs regular blood monitoring

Cyclophosphamide – one used if there is severe organ involvement
has side effect of – infertility

Question 18

Name and explain the mechanism of action of two new treatments for severe disease.

Answer 18

1. Mycophenolate mofetil
   - Reversible inhibitor of inosine monophosphate dehydrogenase
   - This is the rate limiting step in de novo purine synthesis
   - Lymphocytes rely heavily on de novo purine synthesis
2. Rituximab
   - Anti-CD20 antibody
   - Causes depletion of B cells
   - Useful in lupus nephritis

both TERATOGENIC so don’t have a baby, bur no effect on fertility

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 and stroke

Question 20

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

Answer 20

Schistocytes (evidence of microangiopathic haemolytic anaemia) 
Teardrop cells  
Spherocytes  
Few leukocytes  
Few platelets

Question 21

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

Answer 21

1. Hypercellular
2. Mesangial proliferation (glomerulus of the kidney, the mesangium is a structure associated with the capillaries. It is continuous with the smooth muscles of the arterioles. It is outside the capillary lumen, but surrounded by capillaries. It is in the middle (meso) between the capillaries (angis).)
3. Crescent development

Question 22

In what race is the prevalence of this disease increased?

Answer 22

Afro carribeans and asians

Question 23

What is the 15 year survival rate if you have nephritis or don’t?

Answer 23

no nephritis- 85%

nerphritis- 60%

Question 24

What factors make the prognosis worse?

Answer 24

black, male,

low socio-economic status

Question 25

What is the criteria for diagnosis?

Answer 25

4 or more of 11 criteria

SOAP BRAIN MD
S-Serositis
O-oral ulcers
A-arthritis
P-Photosensitivity

B-Blood (all low)
Renal-proteinuria
Immunological- ANA, anti-dsDNA
N-neurological-seizures/psychosis

M-Malar rash
D- discoid rash

Question 26

What are some other features of lupus not mentioned already?

Answer 26

Inflammation kidney, CNS, heart, lungs
Accelerated atherosclerosis
Vasculitis