7. Systemic lupus erythematosus Flashcards
What gender and ethnicities does SLE mainly affect?
- Females
* Afro-caribbeans, Asians and Chinese
What does SLE predominantly affect?
Joints and skin
What main symptoms do mild SLE disease patients have?
Rash and arthritis
Which genes may impact SLE pathogenesis?
Fc receptors, IRF5, CTLA4, MHC class II
How does SLE present?
- Can be vague initially
- Malaise, fatigue, fever, weight loss
- Lymphadenopathy
What are the specific (and other non-specific) features of SLE?
- Butterfly rash (malar rash)
- Alopecia
- Arthralgia
- Raynaud’s phenomenon
(other non-specific:
• Inflammation of the kidney, CNS, heart and lungs
• Accelerated atherosclerosis
• Vasculitis)
List the criteria that a patient must have at least 4/11 of, for the diagnosis to point towards lupus?
- S - serositis (pleuritis or pericarditis)
- O - oral ulcers
- A - arthritis
- P - Photosensitivity
- B - blood (haematological) disorder
- R - renal disorder (proteinuria)
- A - antinuclear antibody raised in titre
- I - immunological disorder (anti-dsDNA)
- N - neurological disorder
- M - malar rash
- D - discoid rash
SOAP BRAIN MD
What does it mean by the fact that the erythematous rash is ‘non-pruritic’?
Doesn’t itch
When is the erythematous rash damaging?
If it extends from the epidermis into the dermis - leads to de-pigmentation and scarring
Where is the malar rash mainly seen?
On the cheeks and bridges of the nose
What triggers SLE?
- Genetic predisposition - not enough on it’s own
- Environmental trigger e.g. EBV - not enough on it’s own
- You need innate immune hyper-activation (hyperactive B cells), so that antibody production over-responds to the combination of the genetic and environmental effects
How do hyperactive B cells lead to the symptoms of SLE?
- Produce autoantibodies
- Further immune activation (cycle)
- Immune complexes generated for systemic deposition
- Leads to intense complement-mediated inflammation and organ damage (e.g. in skin and kidneys)
How does the abnormal clearance of apoptotic cells lead to complement activation?
=> dendritic cell uptake of autoantigens and activation of B cells
=> B cell Ig class switching, affinity maturation
=> IgG autoantibodies
=> immune complexes
=> complement activation
What is the differential diagnosis for SLE?
- ANA (anti-nuclear antibody) positive - immunofluorescence
- Other autoimmune connective tissue disease
- Cutaneous lupus
- Drug induced lupus - symptoms will stop after cessation of drug e.g. hydrazine
What type of staining are you more likely to see in SLE and systemic sclerosis?
- SLE - homogenous nuclear staining
* Systemic sclerosis - nucleolar pattern
What specific anti-nuclear antibodies point towards SLE?
- Anti-dsDNA antibodies and Sm
- Anti-Sm antibodies
- Anti-Ro and/or La antibodies
Which anti-nuclear antibodies can cross the placenta and what affect does this have?
- Anti-Ro
* Cause heart block in the foetus
What 3 lab test show the patient has active lupus?
- High titre ANA
- Hight titre anti-dsDNA antibody
- Low C3/C4
Describe the haematological features in SLE
- Lymphopaenia - low lymphocyte count
- Anaemia (autoimmune haemolytic)
- May have leukopenia and thrombocytopenia - life threatening
Describe the renal features of SLE
- Proteinuria and haematuria
- Absence of infection in conjunction with these are indicative of nephritis
- Active urinary sediment
What do SLE patients generate more apoptotic cells on the skin in response to?
UV light
What 3 groups can SLE be divided in?
- Mild - joint +/- skin involvement
- Moderate - inflammation of other organs
- Severe - severe inflammation of vital organs
How do you treat mild SLE?
- Paracetamol or NSAIDs
- Monitor kidney function
- Hydroxychloroquine if athropathy gets worse
- Topical corticosteroid for rash
How do you treat moderate SLE?
- Corticosteroids - start high initial dose
* Then give IV methylprednisolone
How do you treat severe SLE?
- Azathioprine - immunomodulatory therapy (steroid-sparing)
* Cyclophosphamide
Give and describe examples of novel treatment of sever SLE
Mycophenolate mofetil
• as effective as cyclophosphamide
• doesn’t risk infertility (but is teratogenic)
• reversible inhibitor of inosine monophosphate dehydrogenase (rate-limiting enzyme in de novo purine synthesis, which lymphocytes are dependent upon)
Rituximab
• anti-CD20
What is the survival of SLE patients without and with nephritis?
- Without nephritis - 85% 15 year survival
* With nephritis - 60% 15 year survival
Is disease more aggressive in males or females?
Males
