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 9:1

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  
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
Apoptotic cells are not cleared properly so they persist and expose their nuclear antigens and autoantibodies are generated against these nuclear antigens
The defect in apoptosis is combined with B cell hyperactivity
The overactive B cells are exposed to the nuclear antigens and the plasma cells begin to produce autoantibodies that circulate and form immune complexes
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 specific for SLE though)
- Antibodies in serum bind nuclear antigens, this is picked up by flourescent labelled antibody

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

Homogenous – DNA
Speckled – antibodies to Ro, La, Sm and RNP
Nucleolar – topoisomerase – scleroderma
Centromere – limited cutaneous scleroderma

Question 8

What conditions are associated with the presence of anti-Ro and 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 (if coupled with leukopenia is life threatening)
Lymphopenia
Normocytic anaemia (AIHA)
Autoimmune haemolytic anaemia

Question 11

What renal changes might occur in SLE? And investigations and next steps

Answer 11

Proteinuria
Haematuria
Active urinary sediment (suggests inflammation)
presence of casts (suggests ongoing inflammation)
- presence of heamaturia and proteinuria without infection is indicative of renal nephritis.
- a renal biopsy and aggressive treatment is needed

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 (severe nephritis, CNS disease (psychosis, fitting), AIHA, TPP, cardiac involemeny, pulmonary disease)

Question 15

Describe the treatment of mild disease.

Answer 15

Paracetamol and NSAIDs if no renal involvement
Hydroxychloroquine (good for arthropathy/arthritis and cutaneous manifestations, side effects in the eye (retinal problems))
Topical corticosteroids for rash
Moniter kidney function

Question 16

Describe the treatment of moderate disease. And what is an indicator for changing treatment?

Answer 16

Indicator: not responding properly to nsaids/hydroxychloroquine and organ threatening disease)
ORAL GLUCORTICOIDS
Start with a HIGH dose and titre downwards
( first line tx is corticosteroids, start with high initial dose to supress disease activity (0.5-1.5mg/kg/day)
- Then give IV methylprednisolone (3 x 0.5-1g /24h)
- inital oral dose of steroids for 4 weeks
- then reduce the dose slowly over 2-3 months, to 10mg/day then to 1mg per month

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 , can have neg impact on livier function and white cell count
Cyclophosphamide – one used if there is severe organ involvement (Intravenously pulsed or oral administration)
- eg in severe nephritis (6x1 monthly intravenous pulses)
Problem – bone marrow supression, infertility, cystitis (acrolein is toxic metbaolite of drug), risk of bladder toxicity and eventual carcinoma

Question 18

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

Answer 18

Mycophenolate mofetil
- as effective as cyclophoshamide but doesnt risk infertility, but it is teratogenic
- however not shown to be as good in treatment of renal function
 Reversible inhibitor of inosine monophosphate dehydrogenase
 This is the rate limiting step in de novo purine synthesis
 Lymphocytes rely heavily on de novopurine synthesis

Rituximab and Belimumab 
 Anti-CD20 antibody
 Causes depletion of B cells  
 Useful in lupus nephritis
- Belumumab blocks Blys - this is a B cell cytokine that drives B cell activity and proliferation

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  
poikilocytosis
anisocytosis
fibrin strands 
thrombocytopenia
Spherocytes  
Few leukocytes  
Few platelets

Question 21

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

Answer 21

Hypercellular
Mesangial proliferation
Crescent development (cresentic glomerulonephritis)

Question 22

Deficiency in what will definetly cause SLE?

Answer 22

complement deficiency (C3 or/and C1q)

Question 23

what genes are suspected to have some comtirbution to SLE?

Answer 23

Fc receptors, IRF5, CTLA4, MHC class II HLA genes, these are all over expressed in patients with SLE

Question 24

what are the diagnostic criteria for SLE?

Answer 24

4 or more out of 11 points towards SLE:

• Malar rash
• Discoid Rash
• photosenstivity
• oral ulcers
• arthritis
• serositis (a) pleuritis or (b) pericarditis
• renal disorder e.g. proteinuria >0.5g/24h
• neurological disorder (e.g seizures/psychosis)
• haematological disorder
• immunologic disorder e.g. anti-dsDNA Abs
• antinuclear antibody in raised titre

Question 25

How do you identify disease severity?

Answer 25

1) identify pattern of organ involvement
2) monitor function of affected organs
- renal: measure BP, U and E, urine sediment and protiencreatinine ratio investigated
- lungs/cvs: lung function and echocardiogram
- examine skin, haematology and eyes (rarely effected)
- take bloods to measure signs of early flare, any alopecia
3) identify pattern of autoantibodies expressed
- anti-dsDNA, anti-Sm indicates renal disease
- anti-cardiolipin antibodies

Question 26

what is meant by mild SLE, moderate SLE, and severe SLE?

Answer 26

Mild - only skin and joint involvement
Moderate - some organ involvement (organ inflammation - pleuritis, pericarditis, mild nephritis)
Severe - severe inflammation of vital organs (severe nephritis, CNS disease (fitting, psychosis), pulmonary disease, cardiac involvement, AIHA autoimmune haemolytic anaemia, thrombocytopenia, TTP (Thrombotic thrombocytopenic purpura)

Question 27

SLE prognosis and survival?

Answer 27

85% 15year survival if no nephritis
60% 15 year survival if have nephritis
- prognosis worst if black and low socio-economic status