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Systemic lupus erythematosus sle

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Systemic lupus erythematosus
(SLE)
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterised by
alternating exacerbations & remissions. There is usually multi-organ involvement during
exacerbations. SLE is fairly common, affecting 1 in 2000 people. It is primarily a disease of
the young to middle aged (the modal age range is 14-50 years). Females outnumber males
(as in most autoimmune diseases) by 10:1, and this is believed to be related to oestrogen
being a triggering factor. People on exogenous oestrogen & male patients with Klinefelter’s
syndrome are also at risk of developing SLE. In America, SLE affects black & Hispanic people
more than white people, but it is rare amongst black people living in Africa. There is less
than 100% concordance in monozygotic twins.
Aetiology
Systemic lupus erythematosus is an autoimmune disease resulting from development of
antibodies against self-antigens. The implicated antigens in the disease are nuclear antigens,
and this is why the disease is mostly not organ specific. The trigger initiating development of
autoantibodies in SLE is unknown. The proposed triggers are:
Heredity. There is 40-60% concordance in identical twins. 1
st
-degree relatives are at
increased risk of developing disease (3% chance), although autoantibodies are
present in up to 20% of these relatives. The implicated HLA molecules are HLA-DR2-5
and HLA-B8. HLA-DR2 molecules are associated with the production of anti-dsDNA
antibodies and are therefore associated more with SLE than the rest. HLA-DR3 is
associated with the production of anti-SS antibodies A & B. HLA-DR4 & HLA-DR5 is
associated with the production of Smith antibodies & anti-ribonucleoprotein
antibodies (anti-RNP).
UV light. UV light induces apoptosis of keratinocytes, thus increasing the risk of
expression of lupus autoantigens. This triggers skin & systemic manifestations.
Dendritic cells, however, are implicated more in this disease.
Drugs & toxins. These conjugate with host antigens in predisposed patients and
cause lupus-like reactions. Examples of such drugs are hydralazine, phenytoin and
isoniazid. Slow acetylators are at increased risk. These diseases do not have
antibodies against double-stranded DNA. The lupus-like symptoms stop after
cessation of the drug.
Hormones. This causes increased incidence of the disease in premenopausal women
and in individuals receiving hormonal replacement therapy. It is also most common
during the patients’ reproductive age. It is thought that oestrogens enhance

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antinuclear antibody formation. Women are prone to getting SLE if they use oral
contraceptives.
Complement deficiency. This is not particularly a trigger, but it is associated with a
100% chance of SLE with anti-dsDNA antibodies. The implicated complement genes
include C1q, C2 and C4.
Polyclonal B-cell stimulation. leading to defective apoptosis. There is also reduction
in suppressor T-cells.
Specific autoantibody production. These are directed at transcription & translation
molecules and nucleosomes. Affinity to self-antigens increases as the disease
progresses.
Exposure to EBV. This is thought to be a possible trigger.
Pathogenesis
There are many proposed mechanisms of development of these antibodies:
1. Defective apoptosis leads to display of cellular antigens on the surface of blebs.
2. Dysregulated lymphocytes target normally-protected intracellular antigens.
3. Disruption of lymphocyte signalling.
Ultimately, the disease is caused by a breakdown of tolerance.
The disease can be a type II hypersensitivity disease (resulting from immunoglobulins
binding to antigens in tissues) or a type III hypersensitivity disease (resulting from
immunoglobulins binding to soluble antigens in serum, with the resulting immune
complexes being deposited in tissues). Localisation of the disease depends on the size of the
antigen, the charge of the molecule, the nature of the antigen and the local concentration of
complement. There is widespread tissue damage due to complement activation in tissues in
which immune complexes have been deposited. The antibodies are formed are against
many antigens. The antigens that are specific for SLE are antibodies against double-stranded
DNA (anti-dsDNA). Non-nucleic acid antibodies are also present. These include anti-
erythrocyte antibodies (causing haemolytic anaemia) and anti-platelet antibodies (causing
thrombocytopenia).
Effects of SLE in various systems
The onset of SLE may be acute or insidious. Patients may have constitutional signs during
exacerbations: fever, weight loss, malaise and lethargy. Patients typically present with multi-
organ dysfunction during remissions. Organ-specific features of SLE are:
Joints & muscles. 90% of patients have polyarthralgia or arthritis that is symmetrical
and mainly affects the small joints. There is usually no joint erosion or deformity
1
in
1
In rare cases, you can get major joint deformity a phenomenon called Jaccoud’s arthropathy.

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Systemic lupus erythematosus (SLE) Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterised by alternating exacerbations & remissions. There is usually multi-organ involvement during exacerbations. SLE is fairly common, affecting 1 in 2000 people. It is primarily a disease of the young to middle aged (the modal age range is 14-50 years). Females outnumber males (as in most autoimmune diseases) by 10:1, and this is believed to be related to oestrogen being a triggering factor. People on exogenous oestrogen & male patients with Klinefelter’s syndrome are also at risk of developing SLE. In America, SLE affects black & Hispanic people more than white people, but it is rare amongst black people living in Africa. There is less than 100% concordance in monozygotic twins. Aetiology Systemic lupus erythematosus is an autoimmune disease resulting from development of antibodies against self-antigens. The implicated antigens in the disease are nuclear antigens, and this is why the disease is mostly not organ specific. The trigger initiating development of autoantibodies in SLE is unknown. The proposed triggers are: • • • • Heredity. There is 40-60% concordance in identical twins. 1st-degree relatives are at increased risk of developing disease (3% chance), although autoantibodies are present in up to 20% of these relatives. The implicated HLA molecules are HLA-DR2-5 and HLA-B8. HLA-DR2 molecules are associated with the production of anti-dsDNA ant ...
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