Systemic Lupus Erythematosus

Question 1

What is SLE and what causes it?

Answer 1

Systemic autoimmune disease

Unknown aetiology - multifactorial genetic (HLA-DR3) and environmental

Question 2

What does SLE affect?

Answer 2

Multi-systems pathology:
CNS            Heart 
Kidney        Blood 
Heart           Skin and Joints
Foetus         Lungs

Chronic and relapsing remitting

Question 3

Describe the epidemiology of SLE?

Answer 3

More likely to affect:

• Female 10:1
• Young age of onset (15-47)
• Afro-caribbean/Asian

Rare

Question 4

Describe the pathogenesis of SLE

Answer 4

Interplay of genetic (HLA DR3/2) and environmental factors (Uv exposure) leading to the body’s immune system producing antibodies against itself. In particular proteins in the cell nucleus.

Hyperactive B-cell/T-cell activation

See slide 8

Question 5

Describe the autoantibody formation in SLE?

Answer 5

1) abnormal clearance of apoptotic cell material
2) Dendritic cell uptake of autoantigens and activation of B cells
3) B cell Ig class switching
4) IgG autoantibodies
5) Immune complexes
6) Complement activation cytokine generation etc

1) UV light causes the release of nuclear antigens. In normal people this is cleared up relatively quickly
2) However people with lupus get blebs forming from these nuclear antigens which are detected by dendritic cells.
3) The DC then present the autoantigens to autoreactive T cells which help B cells to produce autoantibodies.
4) autoantibodies cause inflammation via the complement activation and the classical pathway.

Question 6

What is the classic presentation SLE?

Answer 6

Malaise, fatigue, fever, weight loss
Lymphadenopathy

Specific features:

• Butterfly rash (malar), alopecia
• Arthralgia
• Raynaud’s phenomenon

Question 7

What is the SLE - ACR criteria?

Answer 7

You need to have 4 or more.

S-Serositis: pleuritis or pericarditis
O-oral ulcers
A-arthritis
P-Photosensitivity

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

M-Malar rash
D- discoid rash

Question 8

What could be the differential diagnosis of SLE?

Answer 8

ANA (antinuclear antibodies) positive due to infection/malignancy/ other autoimmune disease
Other autoimmune CTD
Cutaneous SLE- without systemic involvement
Drug induced Lupus- procanamide, hydrazine, quinidine, isonizaide

Question 9

What are the SLE laboratory tests which can be carried out?

Answer 9

Antinuclear antibodies:
ANA relatively non-specific, pattern important
• Homogenous - Antibodies to DNA [SLE]
• Speckled - Abs to Ro, La, Sm, RNP [SLE]
• Nucleolar - topoisomerase - [scleroderma]
• Centromere - limited cutaneous [scleroderma]

Anti-dsDNA and Sm:
• More specific but less sensitive for SLE

Anti-Ro and/or La:
• Common in subacute cutaneous LE
• Neonatal lupus syndrome & Sjögren’s

Other tests:
 • Increased complement consumption = low C3 and C4
 • Anti-cardiolipin antibodies
 • Lupus anticoagulant
 • ß1 glycoprotein

Haematology:
• Lymphopaenia, normochromic anaemia
• Leukopaenia, AIHA, thrombocytopaenia

Renal:
• Proteinuria, haematuria
• Active urinary sediment

Question 10

How do you assess the severity of SLE?

Answer 10

1. Identify pattern of organ involvement
2. Monitor function of affected organs
   • Renal - BP, U & E, urine sediment + Prot:Crea ratio
   • Lungs/CVS - lung function, echocardiography
   • Skin, haematology, eyes
3. Identify pattern of autoantibodies expressed

• Anti-dsDNA, anti-Sm - renal disease
• Anti-cardiolipin antibodies

Question 11

How can SLE be divided into?

Answer 11

MILD:
- joint +/- skin involvement

MODERATE:
- inflammation of other organs pleuritis, pericarditis, mild nephritis

SEVERE:
 - severe inflammation in vital organs
	• severe nephritis		          
	• CNS disease
	• pulmonary disease
	• cardiac involvement
	• AIHA, Thrombocytopaenia, TTP

Question 12

What is the treatment for mild SLE?

Answer 12

A. Paracetamol +/- NSAID
• Monitor renal function

B. Hydroxychloroquine
• arthropathy
• cutaneous manifestations
• mild disease activity

C. Topical corticosteroids

Question 13

What is the treatment for moderate SLE?

Answer 13

Oral steroids or IV methylprednisolone (0.5-1g OVER 3 days)

+ Immunosupressants - severe organ disease

• Cyclophosphamide
• Mycofenalate Mofitil (MMF)
• Rituximab (anti-CD20 monoclonal anti-body) for Lupus Nephritis

Maintenance treatment with low dose oral steroids (<5mg/day) and immunosuppressants (methotrexate, azathioprine or MMF)

Question 14

What is the prognosis of SLE?

Answer 14

15 year survival: No nephritis 85%, nephritis 60%

Prognosis is worse, if you are black, male, low socio-economic background

Question 15

What is the bimodal mortality pattern of SLE?

Answer 15

Early 	
Active lupus
 - Renal failure
 - CNS disease
 - Infection

Late
- Myocardial infarction