Systemic Lupus Erythematosus Flashcards
what is SLE?
rare disease and is part of a family of overlapping chronic autoimmune diseases
shows type 3 hypersensitivity (immune complexes) and type 2 (antibodies against RBC, WBC, platelets leading to pancytopenia)
examples of autoimmune diseases in the family that SLE is part of?
RA
Sjogren’s syndrome
dermatomyositis, polymyositis
systemic sclerosis.
who does SLE affect mostly?
female (9:1)
15-40 years
Afro-carribean, Far East Asian, Asian
what does SLE primarily affect?
joints and skin and kidenys
– also affects lungs and has unique haematology
what are the genetic associations of SLE?
- Multiple genes: Fc receptors, IRF5, CTLA4, MHC class 2 HLA genes (DR3)
- Complement deficiency: C1q and C3.
what is the (general) presentation of SLE?
Malaise fatigue fever weight loss lymphadenopathy (lymphomas excluded).
what are specific features of SLE?
Butterfly rash
alopecia
arthralgia
Raynaud’s phenomenon.
what are some severe presentations of SLE?
o Inflammation of the kidney, CNS, heart & lungs.
o Accelerated atherosclerosis.
o Vasculitis.
what is the cause of autoantigens production in SLE?
there is impaired clearance associated with inflammation of apoptotic bodies. They linger in the body and expose nuclear antigens which then generate autoantigens
what is the main driver of SLE?
immune complexes
these bind to endothelial cell to cause local inflammation and activate enzymes after complement activation to cause cell apoptosis
what causes the formation of immune complexes?
- dendritic cells take up autoantigens
- overactive B cells exposed to auto antigens (and activated)
- plasma cells form IgG autoantibodies that form immune complexes (ab-ag)
what is the effect of immune complexes?
deposit in tissues (kidneys/skin mainly) and then activates complement in the tissues
summary of auto-antibody formation summary
- Abnormal clearance of apoptotic bodies.
- Dendrites take up autoantigens –>b-cell activation.
- B-cell Ig-class switch and affinity maturation.
- IgG-autoantibodies.
- Immune complexes.
- Complement activation via classical pathway.
how can SLE be tested for in the lab?
check for
- antinuclear antibodies
- anti dsDNA antibodies
if ANAs present, they will bind to the cell’s nuclear antigens
fluorescently labelled AB is added that binds to ANAs and you observe the pattern of attachment
what other tests can used?
anti-dsDNA and Sm (more specific) anti-Ro and/or La increased complement consumption normocytic anaemia haematology and renal
why might complement consumption be measured to check activity of SLE?
patients with active lupus will have more complement bound to immune complexes and so the blood complement will be LOW in active lupus
why may SLE patients present with autoimmune haemolytic anaemia?
ABs bind to RBC surfaces and they are extravascularly removed in the spleen.
how is the severity of SLE assessed?
- Identify pattern of organ involvement.
- Monitor function of affected organs:
a. Renal
– BP, U&E, urine sediment GFR.
b. Lungs/CVS
– lung function tests, echocardiography. - Identify the patterns of autoantibodies expressed.
a. Anti-dsDNA, anti-Sm
– high levels of these ABs can predict renal disease.
b. Anti-cardiolipin antibodies.
what will happen to the erythrocyte sedimentation rate in disease that is become severe?
increase
what is importance of picking up symptoms early?
so less damage to organs systems occur
in what stage of disease severity is there organ involvement?
moderate to severe
mild has no organ involvement
what is the treatment for mild SLE?
Paracetamol ± NSAIDs.
Hydroxychloroquine (for the rash)
Topical corticosteroids.
what are the severities of SLE and what is involved in each?
mild–> joint +/- skin
moderate–> inflammation of organs, pleuritis, pericarditis
severe–> severe inflammation of vital organs
what is the treatment for moderate SLE?
Hydroxychloroquine and NSAIDs will stop working in moderate disease.
Switch from topic to oral glucocorticoids
High dose and titrate down
why is a high dose given for moderate SLE? what can be done instead?
o High dose needed to supress disease activity but also is very toxic so can give the corticosteroids with steroid-sparing agents to lower the dose required.
what are the 2 drugs given in severe SLE?
Azathioprine – a steroid-sparing drug
Cyclophosphamide – only used in SEVERE organ involvement
- mycophenolate mofetil
- rituximab
what is the side effect of Azathioprine?
risk of neutropenia and bone marrow suppression so requires blood monitoring.
what is the side effect of Cyclophosphamide?
infertility
why is azathioprine a favourable option?
safe during pregnancy as it is steroid sparing
what is the prognosis of SLE?
15 year survival
o No nephritis = 85%.
o Nephritis = 60%.
when is prognosis worse?
black, male, low socio-economic background/status.
what are the two peaks in SLE mortality?
o Early death – renal failure, CNS disease, infection.
o Late death – MI, stroke.
what can be seen on a blood film in SLE?
Shistocytes.
Spherocytes.
Tear drop cells.
Few – leukocytes and platelets
what can be seen in renal biopsy in SLE?
Hyper-cellular – more cells than normal.
Mesangial proliferation.
Crescent development – inflammatory cells that have migrated into the glomerulus.
Rapidly proliferating glomerulonephritis.
which antibody in SLE is specific to the disease?
anti dsDNA antibodies
which antibody is less specific to the disease?
anti-nuclear antibodies
which HLA defect leads to SLE?
HLA DR3
