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     (SLE) is a multiorgan system autoimmune disease with numerous immunological
and clinical manifestations. It is characterized by an autoantibody response to nuclear and cytoplasmic antigens. The
disease mainly involves the skin, joints, kidneys, blood cells, and nervous system. Diagnosing and managing SLE in
the emergency department can be very challenging if it is not considered in one's differential diagnosis. Also, the
laboratory testing of SLE may be unavailable on an emergent basis.

  
 

Systemic lupus erythematosus (SLE) is a multifactorial disease involving genetic, environmental, and hormonal
factors. Its precise pathogenesis is unclear. There is growing evidence in favor of a clearance deficiency of apoptotic
cells as the core mechanism in the pathogenesis of SLE.Defective clearance of apoptotic cells causes secondary
necrosis with release of intracellular content and inflammatory mediators. Macrophages respond and present self-
antigens to T and B cells

Pathogenic autoantibodies are the primary cause of tissue damage in patients with lupus. The production of these
antibodies arises by means of complex mechanisms involving every key facet of the immune system.The abnormal
cellular and humoral response to the formation of these autoantibodies is modulated by genetic, environmental, and
hormonal factors:

Causes

Despite the dramatic rise in Lupus research in recent years, the exact cause of the disease remains unknown. Indeed,
consensus is still lacking on whether Lupus is a single condition or a group of related diseases. SLE is a chronic
inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement,[9]
characterized by the body's production of antibodies against the nuclear components of its own cells. There are three
mechanisms by which lupus is thought to develop: genetic predisposition, environmental triggers and drug reaction
(drug-induced lupus).

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The first mechanism may arise genetically. Research indicates that SLE may have a genetic link. Lupus does run in
families, but no single "lupus gene" has yet been identified. Instead, multiple genes appear to influence a person's
chance of lupus developing when triggered by environmental factors. The most important genes are located on
chromosome 6, where mutations may occur randomly (@ ) or be inherited. Additionally, people with SLE have
an altered RUNX-1 binding site, which may be either cause or contributor (or both) to the condition. Altered binding
sites for RUNX-1 have also been found in people with psoriasis and rheumatoid arthritis.

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The second mechanism may be due to environmental factors. These factors may not only exacerbate existing lupus
conditions, but also trigger the initial onset. They include certain medications (such as some antidepressants and
antibiotics), extreme stress, exposure to sunlight, hormones, and infections. Some researchers have sought to find a
connection between certain infectious agents (viruses and bacteria), but no pathogen can be consistently linked to
the disease. UV radiation has been shown to trigger the photosensitive lupus rash, but some evidence also suggests
that UV light is capable of altering the structure of the DNA, leading to the creation of autoantibodies. Some
researchers have found that women with silicone gel-filled breast implants have produced antibodies to their own
collagen, but it is not known how often these antibodies occur in the general population and there is no data that
show these antibodies cause connective tissue diseases such as lupus.

   

Drug-induced lupus erythematosus is a reversible condition that usually occurs in patients being treated for a long-
term illness. Drug-induced lupus mimics systemic lupus. However, symptoms of drug-induced lupus generally
disappear once a patient is taken off the medication which triggered the episode. There are about 400 medications
currently in use that can cause this condition, though the most common drugs are procainamide, hydralazine and
quinidine.

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In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell
nucleus. SLE is triggered by environmental factors that are unknown.

"All the key components of the immune system are involved in the underlying mechanisms" of SLE, according to
Rahman, and SLE is the prototypical autoimmune disease. The immune system must have a balance (homeostasis)
between being sensitive enough to protect against infection, and being too sensitive and attacking the body's own
proteins (autoimmunity). From an evolutionary perspective, according to Crow, the population must have enough
genetic diversity to protect itself against a wide range of possible infection; some genetic combination's result in
autoimmunity. The likely environmental triggers include ultraviolet light, drugs, and viruses. These stimuli cause the
destruction of cells and expose their DNA, histones, and other proteins, particularly parts of the cell nucleus.
Because of genetic variations in different components of the immune system, in some people the immune system
attacks these nuclear-related proteins and produces antibodies against them. In the end, these antibody complexes
damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the
cause of SLE. Researchers are now identifying the individual genes, the proteins they produce, and their role in the
immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break
each of those links. [10][11][12]

SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II
involvement.[13]

c s a symptoms

SLE is one of several diseases known as the great imitator[17] because its symptoms vary so widely it often mimics
or is mistaken for other illnesses, and because the symptoms come and go unpredictably. Diagnosis can be elusive,
with patients sometimes suffering unexplained symptoms and untreated SLE for years. Common initial and chronic
complaints are fever, malaise, joint pains, myalgias and fatigue. Because they are so often seen with other diseases,
these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other
signs and symptoms (below), however, they are considered suggestive.

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Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic
testing for SLE.Several techniques are used to detect ANAs.Clinically the most widely used method is indirect
immunofluorescence.The pattern of fluorescence suggests the type of antibody present in the patient's serum.

ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may
occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA
(dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced lupus).
Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only
0.5% of people without SLE.[10] The anti-dsDNA antibody titers also tend to reflect disease activity, although not in
all cases.[10] Other ANA that may occur in SLE sufferers are anti-U1 RNP (which also appears in systemic
sclerosis), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome). SS-A
and SS-B confer a specific risk for heart conduction block in neonatal lupus.[22]

Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by
the immune system), electrolytes and renal function (disturbed if the kidney is involved), liver enzymes, complete
blood count and recently By proteomics, we can directly detect proteins as gene products as well as their alterations
by post-translational modification and internal abscission which are characteristically observed in proteins.[23]

Previously, the lupus erythematosus (LE) cell test was not commonly used for diagnosis because those LE cells are
only found in 50±75% of SLE cases, and are also found in some people with rheumatoid arthritis, scleroderma, and
drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical
significance.[24]

As a summary:

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