Systemic lupus erythematosus Flashcards
Definition
A multisystem autoimmune disease that is characterised by autoantibody production against a number of nuclear and cytoplasmic autoantigens
Aetiology
Unknown aetiology for sure, but associated with certain factors.
Hereditary:
- higher concordance rate in identical twins compared to non identical twin
Genetics:
- Genes linked to the development of SLE include HLA-BB, HLA-DR3 and HLA-A1
Sex hormone status:
- The higher incidence in pre-menopausal women and males with Klinefelter’s (XXY) syndrome
Drugs:
- Hydralazine, isoniazid, procainamide and penicillamine can cause mild lupus-like syndrome
Ultraviolet light:
- Can trigger flares of SLE, especially in the skin
Exposure to Epstein-Barr virus:
- Has been suggested as a trigger for SLE
Epidemiology
Incidence of 4 per 100’000
Disease mostly of young women
Peak age of onset 20-40
Affects 0.1% of the population but is more common
Pathophysiology
Injury to the bodies own cells, meaning there is damaged to their proteins and DNA.
When cells are damaged they can try and repair themselves, if they cant they undergo programmed cell death (apoptosis)
When cells undergo apoptosis, internal proteins are displayed on their surface blebs
Normal response:
– when the immune system (macrophages) clear up the apoptotic cells.
Response in SLE:
– where apoptotic cells and cell fragments are cleared inefficiently by phagocytes
– if they aren’t cleared efficiently, then nuclear material is exposed to the immune system which becomes sensitised, meaning that the immune system may eventually mount an attack on its own cells
Pathophysiology
Injury to the bodies own cells, meaning there is damaged to their proteins and DNA.
When cells are damaged they can try and repair themselves, if they cant they undergo programmed cell death (apoptosis)
When cells undergo apoptosis, internal proteins are displayed on their surface blebs
Normal response:
– when the immune system (macrophages) clear up the apoptotic cells.
Response in SLE:
– where apoptotic cells and cell fragments are cleared inefficiently by phagocytes
– if they aren’t cleared efficiently, then nuclear material is exposed to the immune system which becomes sensitised, meaning that the immune system may eventually mount an attack on its own cells
People with SLE are thought to have a deficiency in some complementary proteins like C1, C2 and C3.
– these are important for the efficient clearing of apoptotic cells.
—- (help with opsonisation)
Process of sensitisation:
– when an immature APC (antigen-presenting cell), notices and picks up the proteins and nuclear material from the apoptotic cells
– these antigens that have been picked up by the APC are then displayed on the surface of the APC
The antigens are presented to T-helper cells in nearby lymphocytes, where they will proliferate into different cells
In the case of SLE:
– IL4 release favours T helper 2 cell maturation
– T helper 2 cells promote the humoral immune response (antibody mediated immune response)
– T helper 2 cells stimulates B cell activation and proliferation
– Activated B cells become plasma cells, which are responsible for the antibodies (in the case of SLE these antibodies are autoantibodies, attacking their own cells and antigens)
– these antibodies that are produced target the antigens presented on the APC that it picked up from the apoptotic cells
– when the autoantibodies come into contact with the nuclear proteins in apoptotic cells, this will trigger the inflammatory response
So eventually the immune cells around the area become sensitised to the antigens, so they can release cytokines, leading to the inflammatory response
These different mechanisms causing inflammation to the surrounding area, causing further organ injury and damage, this will further cause a cascade of damaged cells and the cycle will continue
Occurs in flare ups:
– once the inflammation settles, through the intrinsic regulation of the immune system, the body will slowly recover
– appears to represent immunological memory of the body
e.g:
– flare ups occur in response to another exposure to the antigen, so triggers of SLE can cause flare ups (sun exposure, genetics, smoking, etc)
Immunological memory:
– long lived plasma cells (bone marrow) can remember the antigen when exposed to it again
Risk factor
Clinical presentation
Musculoskeletal (90% of cases):
– symmetrical small joint arthralgia
– myalgia
– aseptic necrosis of the hip or knee
Skin (85%):
– ‘butterfly’ rash- erythramatous rash on cheeks and bridge of nose
– alopecia
– photosensitivity
Nervous system (60%):
– epilepsy
– migraine
– aseptic meningitis
Lungs (50%):
– pleural effusions
Kidneys (30%):
– glomerulonephritis
Heart and CVS (25%):
– Pericarditis
– thrombosis- arterial and venous
– accelerated atherosclerosis
GI system:
– mouth ulcers
Blood:
– anaemia
General:
– tiredness
– fever
– depression
– weight loss
Investigations
Blood tests:
– normally shows normochromic and normocytic anaemia
– raised ESR, CRP usually normal unless there is a coexisting infection
Serum compliment C3 and C4 are reduced
Treatment
Depends on the symptoms and severity of the disease
– pts should be advised to avoid excessive sunlight or stop smoking and reduce their cardiovascular risk factors
- NSAID’s are useful for patients with mild disease and with arthralgia
– Corticosteroids, mainstay of treatment, particularly in moderated to severe disease
– immunosuppressive usually in combination with corticosteroids, used in patients with severe manifestations
Prognosis
Disease is characterised by relapses and remissions even in severe disease
10 year survival is about 90%, although much lower if there is major organ involvement
