SLE

Question 1

What is SLE?

Answer 1

Systemic Lupus erythematosus (SLE) is a chronic multi-systemic autoimmune disease of unknown cause that most commonly affects women during their reproductive years. Since it can affect any organ system, its presentation and course are highly variable. The disease is characterised by the presence of antinuclear antibodies (ANA). There are other types of lupus (other than systemic), for instance discoid lupus, drug-induced lupus and overlap syndromes.

Question 2

Describe the pathophysiology of SLE?

Answer 2

• Although the specific cause of SLE unknown, multiple factors are associated including genetic and environmental factors such as oxidative stress, UV light exposure and drugs.
• Many innate an acquired immune disturbances occur in SLE which results in development of autoantibodies and autoreactive T-cells.
• Defective clearance of apoptic cells and immune complexes also contribute and activation of the complement system plays a role in tissue damage
• Antiphospholipids antibodies are a specific family of autoantibodies directed against anionic phospholipids located in cell membranes.

Question 3

What are the risk factors of SLE?

Answer 3

Females more likely

Increases in women of child bearing age (15-45)

More common in Afro-Caribbean and Asians

Minocycline, isoniazid, terbinafine, phenytoin, carbamazepine and sulfasalazine can cause drug-induced lupus
May be an important trigger of SLE

Genetic factors include: HLA, complement, Fc gamma receptor, cytotoxic T-lymphocyte antigen-4 and cytokine genes

Smoking is linked not only to the development of the SLE but also to the prognosis

Question 4

What causes lupus?

Answer 4

Alter gene expression leads to formation of more nucleic acids
Complement activation – damage to skin

Antibodies to self (autoantibodies)
Including
- Genetic material eg DNA, histones Extractable nuclear proteins
- eg Ro, La, RNP, Sm Cytoplasmic proteins
- Membrane phospholipids

The role of cell death (apoptosis) 
Basically........Everything 
-	Development of body structures 
-	Tissue remodelling
-	Selection of immune cells
-	Blood cell turn-over eg after infection etc etc 

Cell death and SLE hypothesis: Too much apoptosis?

• High levels of apoptotic cells after flares
• Free DNA/nucleosomes in blood
• Haematoxylin bodies (apoptotic blebs) in glomeruli.

Apoptosis and lupus

• In general apoptosis functions normally in SLE
• But fragments of apoptotic cells are found due to deficient clearance of apoptotic cells when in large amounts eg infection, sunburn
• This leads to processing of cellular material as if it is foreign which results in antibody formation to self-antigens

Question 5

What are the Non-specific clinical features ?

Answer 5

• Fatigue – nobody understands why this occurs
• Muscle pains
• Lymphadenoapthy
• Fever
• Loss of appetite
• Weight loss

Question 6

What are the 11 CRITERIA for SLE?

Answer 6

American College of Rheumatology - Classification Criteria for SLE - (>4 of 11)
Remember by using acronym

SOAP BRAIN MD

Serotosis
Oral ulcers
Photosensitvity
Blood disorders
ANA positivity
Immunological disorder
Neurological disorder
Malar Rash
Discoid Rash

Question 7

What lab tests need to be done for the diagnosis?

Answer 7

Blood tests

• FBC – anaemia, leucopoenia (lymphenia and neutropenia), thrombocytopenia and raely pancytopenia
• Activated prothrombin time
• ESR and CPR – elevated
• Immunology – ANA antibodies. dsDNA (highly specific), smith antigen (highly specific) positive
• Urea and electrolytes – elevated in renal disease

Urinalysis

Chest X ray

Renal Function

Complement

APTT, Lupus anticoagulant

Cardiolipin antibodies

Question 8

What advice would you provide for someone with SLE?

Answer 8

• Advice for all
o Sunblock Factor 50 – should be on repeat prescription
o Contraception – oestrogen likely to be causing. Recommend progesterone only pill to avoid any contraception which includes oestrogen
o Plan pregnancy – if on cytotoxic drugs. Oestrogen can exacerbate lupus disease, so barrier methods are preffered of progesterone only pills.
o Good diet – low fat, low sugar
o Exercise
o Infections should be avoided and treated promptly.
o Flare
o Smoking cessation

Question 9

What pharmacological treatment is available for lupus?

Answer 9

• Anti-inflammatory drugs for short term – NSAIDs are ok but not for long term.
o e.g. Neurofen / Ibuprofen (care!)
• Antimalarial –
o e.g. hydroxychloroquine - can affect retina, irreversible so can lose vision (very rare – only occurs with cumulative exposure?) – they need to have an opticianal review every year? mepacrine – causes yellow tint
• Steroids – local (cream, inhaled, joint injection) or low dose tablets or injection in muscle – can lead to cushings, worsen diabetes, shingles, steroid induced sarcosis, affect growth in children, risk of infection, loss of bone density (osteopenia/osteoporosis)

• Steroids e.g. prednisolone Oral, IM or intravenous
• Azathioprine oral continuous (steroid sparing agent)
• Methotrexate weekly oral/IM/subcutaneous (steroid sparing agent)
• Ciclosporin A/Tacrolimus oral continuous
• Mycophenolate mofetil Oral (steroid sparing agent)
• Cyclophosphamide IV pulse (oral) – for patients with severe renal, cardiac or neurological involvement or associated systemic vasculitis.
• Rituximab IV
• Belimumab IV