By

Maram Ali Albalawi

Sarah alatwi
Shog Ali Homadi
Ebtihaj Thamer Alenizi
Ezdehar Shaker
Hanan Hamid
Jawaher Frej
Ranay khalf

Systemic lupus erythematosus

Contents:
- Definition.4
- History of the disease...4
- Clinical manifestations.7
- Etiology.8
- Pathophysiology...11
- Diagnosis.15
-Assessment and Diagnostic Findings 18
- Prevention .18
- Treatments..19
- Approach considerations. 21
- Complications..23
- Prognosis .23
- Epidemiology24
- medical management.24
- nursing management..25
- Patient education25
- references

.27

Introduction:
inflammatory autoimmune collagen disease resulting from disturbed immune
regulation that causes an exaggerated production of autoantibodies

Definition :
often abbreviated as SLE or lupus, is a systemic autoimmune disease (or
autoimmune connective tissue disease) in which the bodys immune system
mistakenly attacks healthy tissue. When the immune system is functioning
normally, it makes proteins called antibodies that protect against pathogens such as
viruses and bacteria. Lupus is characterized by the presence of antibodies against a
persons own proteins; these are most commonly anti-nuclear antibodies, which are
found in nearly all cases. These antibodies leading to inflammation. Although the
underlying cause of autoimmune diseases is unknown, most believe that lupus
results from both genetic and environmental stimuli.
There are many kinds of lupus. The most common type is systemic lupus
erythematosus (SLE), which affects many internal organs in the body. SLE most
often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous
system. The course of the disease is unpredictable, with periods of illness (called
flares) alternating with remissions. The disease occurs nine times more often in
women than in men, especially in women in child-bearing years ages 15 to 35, and
is also more common in those of non-European descent.
While there is no cure for SLE, it is treated with immunosuppression, mainly with
cyclophosphamide, corticosteroids and other immunosuppressants. The goal of
these treatments is to keep symptoms under control. SLE can be fatal. The leading
cause of death is from cardiovascular disease due to accelerated atherosclerosis.
Survival for people with SLE in the United States, Canada, and Europe has risen to
approximately 95% at five years, 90% at 10 years, and 78% at 20 years,and now
approaches that of matched controls without lupus.
Childhood systemic lupus erythematosus generally presents between the ages of 3
and 15, with girls outnumbering boys 4:1, and typical skin manifestations being
butterfly eruption on the face and photosensitivity. Lupus is Latin for wolf. In the
18th century, when lupus was just starting to be recognized as a disease, it was
thought that it was caused by a wolf's bite.This may have been because of the
distinctive rash characteristic of lupus. (Once full-blown, the round, disk-shaped
rashes heal from the inside out, leaving a bite-like imprint.

History of the diseas :

The history of SLE can be divided into three periods: classical, neoclassical, and
modern. In each period, research and documentation advanced the understanding
and diagnosis of SLE, leading to its classification as an autoimmune disease in
1851, and to the various diagnostic options and treatments now available to SLE
patients. The advances made by medical science in the diagnosis and treatment of
SLE has dramatically improved the life expectancy of a person diagnosed with
SLE.
_ Etymology
There are several explanations ventured for the term lupus erythematosus. Lupus is
Latin for wolf,and "erythro" is derived from , Greek for "red." All
explanations originate with the reddish, butterfly-shaped malar rash that the disease
classically exhibits across the nose and cheeks.
In various accounts, some doctors thought the rash resembled the pattern of fur on
a wolf's face. More likely is that it is derived from the similarity in distribution to
lupus vulgaris or chronic facial tuberculosis where the lesions are ragged and
punched out and are said to resemble the bite of a wolf.
Another account claims that the term "lupus" did not come from Latin directly, but
from the term for a French style of mask that women reportedly wore to conceal
the rash on their faces. The mask is called a "loup," French for "wolf."
_ Classical period
The classical period began when the disease was first recognized in the Middle
Ages. The term lupus is attributed to 12th-century Italian physician Rogerius
Frugard, who used it to describe ulcerating sores on the legs of patients. No formal
treatment for the disease existed and the resources available to physicians to
relieve the suffering of their patients was limited.
_ Neoclassical period
The neoclassical period began in 1851 when the skin disease now known as
discoid lupus was documented by French physician, Pierre Cazenave. Cazenave
termed the illness lupus and added the word erythematosus to distinguish this
disease from other illnesses that affected the skin except they were infectious.
Cazenave observed the disease in several patients and made very detailed notes to
assist others in its diagnosis. He was one of the first to document that lupus
affected adults from adolescence into the early thirties and that the facial rash is its
most distinguishing feature.
Research and documentation of the disease continued in the neoclassical period
with the work of Ferdinand von Hebra and his son-in-law, Moritz Kaposi. They
documented the physical effects of lupus as well as some insights into the
possibility that the disease caused internal trauma. von Hebra observed that lupus
symptoms could last many years and that the disease could go "dormant" after
years of aggressive activity and then re-appear with symptoms following the same

general pattern. These observations led Hebra to term lupus a chronic disease in
1872.
Kaposi observed that lupus assumed two forms: the skin lesions (now known as
discoid lupus) and a more aggravated form that affected not only the skin but also
caused fever, arthritis, and other systemic disorders in patients. The latter also
presented a rash confined to the face, appearing on the cheeks and across the
bridge of the nose; he called this the "butterfly rash". Kaposi also observed those
patients who developed the "butterfly rash" (or malar rash) often were afflicted
with another disease such as tuberculosis, anemia, or chlorisis which often caused
death.Kaposi was one of the first persons to recognize what is now termed
systemic lupus erythematosus in his documentation of the remitting and relapsing
nature of the disease and the relationship of skin and systemic manifestations
during disease activity.
The 19th century's research into lupus continued with the work of Sir William
Osler who, in 1895, published the first of his three papers about the internal
complications of erythema exudativum multiforme. Not all the patient cases in his
paper suffered from SLE but Osler's work expanded the knowledge of systemic
diseases and documented extensive and critical visceral complications for several
diseases including lupus. Noting that many patients with lupus had a disease that
not only affected the skin but many other organs in the body as well, Osler added
the word "systemic" to the term lupus erythematosus to distinguish this type of
disease from discoid lupus erythematosus. Osler's second paper noted that
reoccurrence is a special feature of the disease and that attacks can be sustained for
months or even years. Further study of the disease led to a third paper, published in
1903, documenting afflictions such as arthritis, pneumonia, the inability to form
coherent ideas, delirium, and central nervous system damage as all affecting
patients diagnosed with SLE.
_ Modern period
The modern period, beginning in 1920, saw major developments in research into
the cause and treatment of discoid and systemic lupus. Research conducted in the
1920s and 1930s led to the first detailed pathologic descriptions of lupus and
demonstrated how the disease affected the kidney, heart, and lung tissue. A major
breakthrough was made in 1948 with the discovery of the LE cell (the lupus
erythematosus cella misnomer, as it occurs with other diseases as well).
Discovered by a team of researchers at the Mayo Clinic, they discovered that the
white blood cells contained the nucleus of another cell that was pushing against the
white's cell proper nucleus. Noting that the invading nucleus was coated with antibody that allowed it to be ingested by a phagocytic or scavenger cell, they named
the antibody that causes one cell to ingest another the LE factor and the two-nuclei

cell result the LE cell.The LE cell, it was determined, was a part of an anti-nuclear
antibody (ANA) reaction; the body produces antibodies against its own tissue. This
discovery led to one of the first definitive tests for lupus since LE cells are found in
approximately 60% of all people diagnosed with lupus. (Note: The LE cell test is
rarely performed as a definitive lupus test today as LE cells do not always occur in
lupus patients and can occur in individuals with other autoimmune diseases. Their
presence can be helpful in establishing a diagnosis but no longer indicates a
definitive SLE diagnosis.
The discovery of the LE cell led to further research and this resulted in more
definitive tests for lupus. Building on the knowledge that those with SLE had autoantibodies that would attach themselves to the nuclei of normal cells, causing the
immune system to send white blood cells to fight off these "invaders", a test was
developed to look for the anti-nuclear antibody (ANA) rather than the LE cell
specifically. This ANA test was easier to perform and led not only to a definitive
diagnosis for lupus but also many other related diseases. This discovery led to the
development of what are now known as autoimmune diseases.
To ensure that the patient has lupus and not another autoimmune disease, the
American College of Rheumatology (ACR) established a list of clinical and
immunologic criteria that, in any combination, point to SLE. The criteria include
symptoms that the patient can identify (e.g. pain) and things that a physician can
detect in a physical examination and through laboratory test results. The list was
originally compiled in 1971, initially revised in 1982, and further revised and
improved in 2009.
Medical historians have theorized that people with porphyria (a disease that shares
many symptoms with SLE) generated folklore stories of vampires and werewolves,
due to the photosensitivity, scarring, hair growth, and porphyrin brownish-red
stained teeth in severe recessive forms of porphyria (or combinations of the
disorder, known as dual, homozygous, or compound heterozygous porphyrias).
Useful medication for the disease was first found in 1894, when quinine was first
reported as an effective therapy. Four years later, the use of salicylates in
conjunction with quinine was noted to be of still greater benefit. This was the best
available treatment until the middle of the twentieth century, when Hench
discovered the efficacy of corticosteroids in the treatment of SLE.

clinical manifestations :
Onset is insidious or acute. SLE can go undiagnosed for many years . The clinical
course is one of exacerbation and remissions .
_ Classic symptoms : fever , fatigue , weight loss , and possibly arthritis , pleurisy
_ Musculoskeletal system : arthralgias and arthritis ( synovitis ) are common
presenting features .

Joint swelling , tenderness , and pain on movement are common , accompanied by

morning stiffness .
_ Integumentary system : several different types are seen ( eg , subacute
cutaneous lupus erythematosus lupus erythematosus [SCLE] discoid lupus
erythematosus [ DLE ]) .
A butterfly rash across the bridge of the nose and cheeks occurs in more than half
of patient and may be a precursor to systemic involvement .
Lesions worsen during exacerbations (flares) and may be provoked by sunlight
or artificial ultraviolet tight .
Oral ulcers and involve buccal mucosa or nard palate .
_Cardiovascular system : pericarditis is the most common clinical cardiac
manifestation. Women who have SLE are also at risk for early atherosclerosis
papular , erythematous , and purpuric lesions may occur on fingers , elbows , toes ,
and extensor surfaces of forearms or lateral sides of hands and may progress to
necrosis .
Varied and frequent neuropsychiatric presentation , generally demonstrated by
subtle changes in behavior or cognitive ability .

Etiology :
The specific causes of systemic lupus erythematosus remain undefined. Research
suggests that many factors, including genetics, hormones, and the environment (eg,
sunlight, drugs), contribute to the immune dysregulation observed in lupus. (See
the diagram below.)

Within the healthy population, a subset of individuals has small amounts of lowtiter antinuclear antibody (ANA) or other autoantibody such as anti-Ro(SSA), antiLa(SSB), or antithyroid antibodies. In lupus, increased production of specific
autoantibodies (anti-dsDNA, anti-RNP, and anti-Smith antibodies) leads to
immune complex formation and tissue damage from direct binding in tissues,
immune complex deposition in tissues, or both.
Evidence suggests that people with systemic lupus erythematosus (SLE) have
antigen-specific antibody responses to DNA, other nuclear antigens, ribosomes,
platelets, erythrocytes, leukocytes, and tissue-specific antigens. The resulting
immune complexes cause widespread tissue damage. Cell-mediated autoimmune
responses also play a pathophysiologic role.
Autoantibody production, by relatively few B lymphocytes, may be a byproduct of
polyclonal B-cell activation in which many more B lymphocytes are activated,
perhaps not in response to specific antigenic stimuli. Data on 3 adolescents with
lupus demonstrated a high percentage of mature naive B cells (25-50% vs 5-20%
in healthy adolescents) producing self-reactive antibodies even before they
participated in an immune response, suggesting defective checkpoints in B-cell
development.[3]

The discovery of viral like particles in lymphocytes in patients with lupus led to
the theory that viral infection causes polyclonal activation in lupus. However, these
particles may simply be breakdown products of intracellular materials. This
assumption was supported by evidence in which specific viruses, such as EpsteinBarr virus and cytomegalovirus, in lupus white blood cells (WBCs), were not
isolated in polymerase chain reaction (PCR) assay. Thus, positive titers to
infectious agents in patients with lupus may be another manifestation of
nonspecific polyclonal activation of B cells, an important point during initial
evaluation and diagnosis. However, viral stimulation of the innate immune system
(dendritic cells), coupled with genetic defects in the innate and adaptive immune
responses, could lead to loss of tolerance and increasingly specific autoantibody
formation.
The presence of measurable autoantibodies implies a loss of tolerance to selfantigens and may include T-lymphocyte abnormalities. Early studies suggested a
loss of T-suppressor function; however, subsequent investigations have centered on
defects of programmed cell death, or apoptosis. This process of programmed cell
death may be dysregulated in lupus, resulting in cells with the potential for selfreactivity persisting instead of undergoing the normal process of apoptosis.
T cells from patients with lupus have been found with increased levels of Bcl-2, a
protein that delays apoptosis. Patients have also been found to have lymphocytes
that underwent increased apoptosis. One explanation may be that in lupus,
lymphocytes that make self-reactive antibodies survive in the host but undergo
increased cell turnover after an inciting trigger, such as a viral infection, begins the
process that manifests as lupus.
Over the past 15 years, studies of lupus have implicated the importance of innate
immunity. Plasmacytoid dendritic cells are decreased in the blood of lupus patients
but are found in high concentration at sites of inflammation such as the kidney and
skin, secreting alpha-interferons.The presence of high concentrations of interferon
in the sera of lupus patients was originally described by Lars Ronnblom and was a
seminal observation of lupus pathophysiologic mechanisms.
Plasmacytoid dendritic cells endocytose immune complexes and nucleic debris
through the Fc gamma-receptor IIa, activating toll-like receptors 7 and 9 and
triggering production of interferon-alpha and other proinflammatory cytokines.
The excess necrotic and apoptotic materials are due to ultraviolet damage, viral
infection, and genetic differences, some of which are listed below and which
include impaired clearance of these materials. Necrotic materials are also due to
neutrophil responses to infection. Neutrophils can extrude their nuclear materials to
form neutrophil extracellular traps or NETosis, immobilizing bacteria and fungi.
NETosis triggers an interferon signal and plasmacytoid dendritic cell activation
that can induce lupus.

Other immunologic mechanisms may also be important, including defects in

macrophage phagocytic activity or handling of immune complexes. In addition,
deficiencies of complement components, including C4, C2, and C1q, have been
associated with lupus, likely due to defective clearance of immune complexes.
Complement receptors may be abnormal in some patients, leading to problems
with clearance of immune complexes and subsequent deposition into tissues. This
may, in association with dyslipoproteinemia, lead to significant vascular
complications.
The predominance of lupus in females suggests sex hormones may play a role in
autoimmune diseases. Research found that patients with lupus did not have
different serum levels of estrogen and prolactin than did controls; however, free
androgen was lower, whereas follicle-stimulating hormone (FSH) and luteinizing
hormone (LH) levels were higher in postpubertal boys and girls with SLE.
Drugs, such as anticonvulsants and antiarrhythmic agents, can also play a role in
the pathogenesis of lupus. These drugs can cause a lupuslike syndrome, which
resolves when the drug is discontinued or can be implicated as the trigger in
systemic lupus. Sun exposure leading to inflammation and apoptosis of skin cells
can also trigger systemic lupus.
_Genetic susceptibility :
The use of microarray technology to detect candidate susceptibility genes has led
to the identification of several potential gene-risk candidates, including the Pselectin gene (SELP), the interleukin-1 receptor-associated kinase 1 gene (IRAK1),
PTPN22, and the interleukin-16, protein tyrosine phosphatase receptor type T, tolllike receptor (TLR) 8, and CASP 10 genes.

pathophysiology :
This disturbance is brought about by some combination of genetic , hormonal ( as
evidenced by the usual onset during the childbearing years ) , and environmental
factors ( sunlight , thermal burns). Certain medication , such as hydralazine
(Apresoline ) , procainamide ( Pronestyl ) , isoniazid or INH ( Nydrazid ) ,
chlorpromazine ( thorazine ) , and some antiseizure medications , have been
implicated in chemical or drug induced SLE .
Specifically , B cells and T cells both contribute to the immune response in SLE .
B cells are instrumental in promoting the onset and flares of the disease .
One manifestation of SLE is abnormalities in apoptosis, a type of programmed cell
death in which aging or damaged cells are neatly disposed of as a part of normal
growth or functioning.
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.

The immune system must balance between being sensitive enough to protect
against infection, and becoming sensitized to attack the body's own proteins
(autoimmunity). During an immune reaction to a foreign stimulus, such as bacteria,
virus, or allergen, immune cells that would normally be deactivated due to their
affinity for self tissues can be abnormally activated by signaling sequences of
antigen-presenting cells. Thus triggers may include viruses, bacteria, allergens (IgE
and other hypersensitivity), and can be aggravated by environmental stimulants
such as ultraviolet light and certain drug reactions. These stimuli begin a reaction
that leads to destruction of other cells in the body and exposure of their DNA,
histones, and other proteins, particularly parts of the cell nucleus. The body's
sensitized B-lymphocyte cells will now produce antibodies against these nuclearrelated proteins. These antibodies clump into antibody-protein complexes which
stick to surfaces and 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.
SLE is a chronic inflammatory disease believed to be a type III hypersensitivity
response with potential type II involvement. Reticulate and stellate acral
pigmentation should be considered a possible manifestation of SLE and high titers
of anti-cardiolipin antibodies, or a consequence of therapy.
_Abnormalities in cell death signaling :
Apoptosis is increased in monocytes and keratinocytes
Expression of Fas by B cells and T cells is increased
There are correlations between the apoptotic rates of lymphocytes and disease
activity.
Necrosis is increased in T lymphocytes.
Tingible body macrophages (TBMs) large phagocytic cells in the germinal
centers of secondary lymph nodes express CD68 protein. These cells normally
engulf B cells that have undergone apoptosis after somatic hypermutation. In some
people with SLE, significantly fewer TBMs can be found, and these cells rarely
contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be
found outside of TBMs.
This material may present a threat to the tolerization of B cells and T cells.
Dendritic cells in the germinal center may endocytose such antigenic material and
present it to T cells, activating them.
Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular
dendritic cells and make this material available for activating other B cells that
may have randomly acquired self-specificity through somatic hypermutation .

Necrosis, a pro-inflammatory form of cell death, is increased in T lymphocytes,

due to mitochondrial dysfunction, oxidative stress, and depletion of ATP.
_Clearance deficiency:
Impaired clearance of dying cells is a potential pathway for the development of this
systemic autoimmune disease. This includes deficient phagocytic activity and scant
serum components in addition to increased apoptosis.
Monocytes isolated from whole blood of SLE sufferers show reduced expression
of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the
monocytes and tingible body macrophages (TBMs), which are found in the
germinal centres of lymph nodes, even show a definitely different morphology;
they are smaller or scarce and die earlier. Serum components like complement
factors, CRP, and some glycoproteins are, furthermore, decisively important for an
efficiently operating phagocytosis. With SLE, these components are often missing,
diminished, or inefficient.
Recent research has found an association between certain lupus patients (especially
those with lupus nephritis) and an impairment in degrading neutrophil extracellular
traps (NETs). These were due to DNAse1 inhibiting factors, or NET protecting
factors in patient serum, rather than abnormalities in the DNAse1 itself.[49]
DNAse1 mutations in lupus have so far only been found in some Japanese cohorts.
The clearance of early apoptotic cells is an important function in multicellular
organisms. It leads to a progression of the apoptosis process and finally to
secondary necrosis of the cells if this ability is disturbed. Necrotic cells release
nuclear fragments as potential autoantigens, as well as internal danger signals,
inducing maturation of dendritic cells (DCs), since they have lost their membranes'
integrity. Increased appearance of apoptotic cells also simulates inefficient
clearance. That leads to maturation of DCs and also to the presentation of
intracellular antigens of late apoptotic or secondary necrotic cells, via MHC
molecules. Autoimmunity possibly results by the extended exposure to nuclear and
intracellular autoantigens derived from late apoptotic and secondary necrotic cells.
B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get
activated by these autoantigens; inflammation and the production of autoantibodies
by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells
has also been observed in people with cutaneous lupus erythematosus (CLE).

_Accumulation in germinal centers :

In healthy conditions, apoptotic lymphocytes are removed in germinal centres
(GC) by specialized phagocytes, the tingible body macrophages (TBM), which is
why no free apoptotic and potential autoantigenic material can be seen. In some
people with SLE, accumulation of apoptotic debris can be observed in GC because
of an ineffective clearance of apoptotic cells. In close proximity to TBM, follicular
dendritic cells (FDC) are localised in GC, which attach antigen material to their
surface and, in contrast to bone marrow-derived DC, neither take it up nor present
it via MHC molecules.
Autoreactive B cells can accidentally emerge during somatic hypermutation and
migrate into the germinal center light zone. Autoreactive B cells, maturation
coincidentally, normally do not receive survival signals by antigen planted on
follicular dendritic cells, and perish by apoptosis. In the case of clearance
deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets
attached to FDC. This serves as a germinal centre survival signal for autoreactive
B-cells. After migration into the mantle zone, autoreactive B cells require further
survival signals from autoreactive helper T cells, which promote the maturation of
autoantibody-producing plasma cells and B memory cells. In the presence of
autoreactive T cells, a chronic autoimmune disease may be the consequence.

_Anti-nRNP autoimmunity:
Autoantibodies to nRNP A and nRNP C initially targeted restricted, proline-rich
motifs. Antibody binding subsequently spread to other epitopes. The similarity and
cross-reactivity between the initial targets of nRNP and Sm autoantibodies
identifies a likely commonality in cause and a focal point for intermolecular
epitope spreading.

_Others:
Elevated expression of HMGB1 was found in the sera of patients and mice with
systemic lupus erythematosus, high mobility group box 1 (HMGB1) is a nuclear
protein participating in chromatin architecture and transcriptional regulation.
Recently, there is increasing evidence HMGB1 contributes to the pathogenesis of
chronic inflammatory and autoimmune diseases due to its proinflammatory and
immunostimulatory properties.

Diagnosis
_ Laboratory tests :
Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (antiENA) form the mainstay of serologic testing for SLE. Several techniques are used
to detect ANAs. Clinically the most widely used method is indirect
immunofluorescence (IF). The pattern of fluorescence suggests the type of
antibody present in the patient's serum. Direct immunofluorescence can detect
deposits of immunoglobulins and complement proteins in the patient's skin. When
skin not exposed to the sun is tested, a positive direct IF (the so-called lupus band
test) is an evidence of systemic lupus erythematosus.
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.The anti-dsDNA antibody titers also tend to reflect disease activity, although
not in all cases.Other ANA that may occur in people with SLE are anti-U1 RNP
(which also appears in systemic sclerosis and mixed connective tissue disease), SSA (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjgren's
syndrome). SS-A and SS-B confer a specific risk for heart conduction block in
neonatal lupus.
Other tests routinely performed in suspected SLE are complement system levels
(low levels suggest consumption by the immune system), electrolytes and kidney
function (disturbed if the kidney is involved), liver enzymes, and complete blood
count.
The lupus erythematosus (LE) cell test was commonly used for diagnosis, but it is
no longer used because the LE cells are only found in 5075% of SLE cases, and
they 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.
_ Diagnostic criteria :
Some physicians make a diagnosis on the basis of the American College of
Rheumatology (ACR) classification criteria. The criteria, however, were
established mainly for use in scientific research including use in randomized
controlled trials which require higher confidence levels, so many people with SLE
may not pass the full criteria.
_ Criteria :
The American College of Rheumatology (ACR) established eleven criteria in
1982,which were revised in 1997[58] as a classificatory instrument to
operationalise the definition of SLE in clinical trials. They were not intended to be
used to diagnose individuals and do not do well in that capacity. For the purpose of
identifying patients for clinical studies, a person has SLE if any 4 out of 11
symptoms are present simultaneously or serially on two separate occasions. Useful
mnemonic for remembering the diagnostic findings or symptoms of SLE is SOAP
BRAIN MD (S=serositis, O=oral ulcers, A=arthritis, P=photosensitivity,
pulmonary fibrosis, B=blood cells, R=renal, Raynauds, A=ANA, I=immunologic
(anti-Sm, anti-dsDNA), N=neuropsych, M=malar rash, D=discoid rash), however,
not in order of diagnostic importance.
1- Malar rash (rash on cheeks); sensitivity = 57%; specificity = 96%.
2- Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%;
specificity = 99%.
3- Serositis: Pleurisy (inflammation of the membrane around the lungs) or
pericarditis (inflammation of the membrane around the heart); sensitivity = 56%;
specificity = 86% (pleural is more sensitive; cardiac is more specific).
4- Oral ulcers (includes oral or nasopharyngeal ulcers); sensitivity = 27%;
specificity = 96%.
5- Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness,
swelling, or effusion; sensitivity = 86%; specificity = 37%.
6- Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of
SLE flareups); sensitivity = 43%; specificity = 96%.
7- Bloodhematologic disorderhemolytic anemia (low red blood cell count) or
leukopenia (white blood cell count<4000/l), lymphopenia (<1500/l) or
thrombocytopenia (<100000/l) in the absence of offending drug; sensitivity =
59%; specificity = 89%. Hypocomplementemia is also seen, due to either
consumption of C3[60] and C4 by immune complex-induced inflammation or to
congenitally complement deficiency, which may predispose to SLE.
8- Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in
urine under a microscope; sensitivity = 51%; specificity = 94%.

9- Antinuclear antibody test positive; sensitivity = 99%; specificity = 49%.

10- Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid
antibody, and/or false positive serological test for syphilis; sensitivity = 85%;
specificity = 93%. Presence of anti-ss DNA in 70% of cases (though also positive
with rheumatic disease and healthy persons).
11-Neurologic disorder: Seizures or psychosis; sensitivity = 20%; specificity =
98%.
_ Other than :
the ACR criteria, people with lupus may also have:
fever (over 100 F/ 37.7 C)
extreme fatigue
hair loss
fingers turning white and/or blue when cold (Raynaud's phenomenon)
_ Criteria for individual diagnosis :
Some people, especially those with antiphospholipid syndrome, may have SLE
without four of the above criteria, and also SLE may present with features other
than those listed in the criteria.
Recursive partitioning has been used to identify more parsimonious criteria.This
analysis presented two diagnostic classification trees:
1- Simplest classification tree: SLE is diagnosed if a person has an immunologic
disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or
LE cells) or malar rash. It has sensitivity = 92% and specificity = 92%.
2- Full classification tree: Uses 6 criteria. It has sensitivity = 97% and specificity =
95%.
Other alternative criteria have been suggested, e.g. the St. Thomas' Hospital
"alternative" criteria in 1998.

Assessment and Diagnostic Findings :

Diagnosis is based on a complete history, physical examination, and blood tests.
No single laboratory test confirms SLE. Blood testing reveals moderate to severe
anemia, thrombocytopenia, leukocytosis, or leukopenia and positive antinuclear
topenia, antibodies. Other diagnostic immunological tests support but do not
confirm the diagnosis.

Prevention :
SLE cannot be prevented, but the consequences can be prevented
As longevity of people with SLE increases, the likelihood of complications also
increases in four areas: cardiovascular disease, infections, osteoporosis, and cancer.
Standard preventive measures, screening for related diseases may be necessary to

deal with the increased risks due to the side effects of medications. Extra vigilance
is considered warranted in particular for cancers affecting the immune system.

Treatment :
The treatment of SLE involves preventing flares and reducing their severity and
duration when they occur.
Treatment can include corticosteroids and anti-malarial drugs. Certain types of
lupus nephritis such as diffuse proliferative glomerulonephritis require bouts of
cytotoxic drugs. These drugs include cyclophosphamide and mycophenolate.
Hydroxychloroquine (HCQ) was approved by the FDA for lupus in 1955. Some
drugs approved for other diseases are used for SLE 'off-label'. In November 2010,
an FDA advisory panel recommended approving belimumab (Benlysta) as a
treatment for the pain and flare-ups common in lupus. The drug was approved by
the FDA in March 2011. N-acetylcysteine has been shown to reverse depletion of
the natural anti-oxidant glutathione and to safely improve disease activity in a
double-blind placebo-controlled pilot study.
_ Medications
Due to the variety of symptoms and organ system involvement with SLE, its
severity in an individual must be assessed in order to successfully treat SLE. Mild
or remittent disease may, sometimes, be safely left untreated. If required,
nonsteroidal anti-inflammatory drugs and antimalarials may be used. Medications
such as Prednisone, Cellcept and Prograf have been used in the past. A number of
potential treatments are in clinical trials.
_ Disease-modifying antirheumatic drugs
Disease-modifying antirheumatic drugs (DMARDs) are used preventively to
reduce the incidence of flares, the process of the disease, and lower the need for
steroid use; when flares occur, they are treated with corticosteroids. DMARDs
commonly in use are antimalarials such as Plaquenil and immunosuppressants (e.g.
methotrexate and azathioprine). Plaquenil (hydroxychloroquine) is an FDAapproved antimalarial used for constitutional, cutaneous, and articular
manifestations. Hydroxychloroquine has relatively few side effects, and there is
evidence that it improves survival among people who have SLE.
Cyclophosphamide is used for severe glomerulonephritis or other organ-damaging
complications. Mycophenolic acid is also used for treatment of lupus nephritis, but
it is not FDA-approved for this indication, and FDA is investigating reports that it
may be associated with birth defects when used by pregnant women.
_ Immunosuppressive drugs
In more severe cases, medications that modulate the immune system (primarily
corticosteroids and immunosuppressants) are used to control the disease and
prevent recurrence of symptoms (known as flares). Depending on the dosage,

people who require steroids may develop Cushing's syndrome, symptoms of which
may include obesity, puffy round face, diabetes mellitus, increased appetite,
difficulty sleeping and osteoporosis. These may subside if and when the large
initial dosage is reduced, but long-term use of even low doses can cause elevated
blood pressure and cataracts.
Numerous new immunosuppressive drugs are being actively tested for SLE. Rather
than suppressing the immune system nonspecifically, as corticosteroids do, they
target the responses of individual [types of] immune cells. Some of these drugs are
already FDA-approved for treatment of rheumatoid arthritis.[69] See also
Belimumab and Atacicept. Lupuzor has given encouraging results in a phase IIb
trial.
_ Analgesia
Since a large percentage of people with SLE suffer from varying amounts of
chronic pain, stronger prescription analgesics (pain killers) may be used if overthe-counter drugs (mainly nonsteroidal anti-inflammatory drugs) do not provide
effective relief. Potent NSAIDs such as indomethacin and diclofenac are relatively
contraindicated for patients with SLE because they increase the risk of kidney
failure and heart failure.
Pain is typically treated with opioids, varying in potency based on the severity of
symptoms. When opioids are used for prolonged periods, drug tolerance, chemical
dependency, and addiction may occur. Opiate addiction is not typically a concern,
since the condition is not likely to ever completely disappear. Thus, lifelong
treatment with opioids is fairly common for chronic pain symptoms, accompanied
by periodic titration that is typical of any long-term opioid regimen.
_ Intravenous Immunoglobulins (IVIGs)
Intravenous immunoglobulins may be used to control SLE with organ
involvement, or vasculitis. It is believed that they reduce antibody production or
promote the clearance of immune complexes from the body, even though their
mechanism of action is not well-understood. Unlike immunosuppressives and
corticosteroids, IVIGs do not suppress the immune system, so there is less risk of
serious infections with these drugs.
_ Lifestyle changes
Avoiding sunlight is the primary change to the lifestyle of SLE sufferers, as
sunlight is known to exacerbate the disease, as is the debilitating effect of intense
fatigue. These two problems can lead to patients becoming housebound for long
periods of time. Drugs unrelated to SLE should be prescribed only when known
not to exacerbate the disease. Occupational exposure to silica, pesticides and
mercury can also make the disease worsen.
_ Kidney transplantation

Kidney transplants are the treatment of choice for end-stage kidney disease, which
is one of the complications of lupus nephritis, but the recurrence of the full disease
is common in up to 30% of patients.
_ Antiphospholipid syndrome
Antiphospholipid syndrome is also related to the onset of neural lupus symptoms
in the brain. In this form of the disease the cause is very different from lupus:
thromboses (blood clots or "sticky blood") form in blood vessels, which prove to
be fatal if they move within the blood stream. If the thromboses migrate to the
brain, they can potentially cause a stroke by blocking the blood supply to the brain.
If this disorder is suspected in patients, brain scans are usually required for early
detection. These scans can show localized areas of the brain where blood supply
has not been adequate. The treatment plan for these patients requires
anticoagulation. Often, low-dose aspirin is prescribed for this purpose, although for
cases involving thrombosis anticoagulants such as warfarin are used.
_ Management of pregnancy
While most infants born to mothers who have SLE are healthy, pregnant mothers
with SLE should remain under medical care until delivery. Neonatal lupus is rare,
but identification of mothers at highest risk for complications allows for prompt
treatment before or after birth. In addition, SLE can flare up during pregnancy, and
proper treatment can maintain the health of the mother longer. Women pregnant
and known to have anti-Ro (SSA) or anti-La antibodies (SSB) often have
echocardiograms during the 16th and 30th weeks of pregnancy to monitor the
health of the heart and surrounding vasculature.
Contraception and other reliable forms of pregnancy prevention is routinely
advised for women with SLE, since getting pregnant during active disease was
found to be harmful. Lupus nephritis was the most common manifestation.

Approach Considerations:
The most important tool in the medical care of the patient with systemic lupus
erythematosus (SLE) is careful and frequent clinical and laboratory evaluation to
tailor the patients medical regimen and to provide prompt recognition and
treatment of disease flare, which is the cornerstone of successful intervention.
Because lupus is a lifelong illness, patients must be indefinitely monitored.
Consideration should be given to the prevention of atherosclerosis and
osteoporosis, because these are long-term consequences of SLE and its treatment.
Moreover, studies have brought attention to the need for the preservation of
gonadal function when gonadotoxic therapies are used to treat severe disease.

Recently, consensus treatment plans have been published for pediatric lupus
proliferative nephritis class III and IV. These consensus treatment plans are
currently being studied in a comparative effectiveness trial.
Newer biologic therapies are looming as potential treatments for lupus, including
B-cell directed therapies, one of which has been approved for use in adult
lupus.This latter therapy is currently being studied in the pediatric population.
Others include T-celldirected therapies, anticomplement therapies, anticytokine
therapies, and peptide manipulation to promote tolerance. Stem cell transplantation
and high-dose immunoablative therapies are also being studied, but it is unclear
whether these therapies confer an advantage. The most recent therapies under trial
are monoclonal antibodies directed again interferon-alpha, which are in phase I and
II clinical trials, while plasmacytoid dendritic cell inhibitors are in development
and in phase I trials.
The need for surgical care depends on the severity of organ involvement and the
need for tissue diagnosis. Usually, SLE is not a surgical condition. If surgery is
necessary, closely monitor the patient for healing and evidence of infection.
_ Activity
Encourage patients with systemic lupus erythematosus to maintain a normal
lifestyle. Exercise is important in maintaining bone density and an appropriate
weight. Caution patients that fatigue and stress have been associated with disease
flares. Caution patients to avoid sunlight and to liberally apply waterproof
sunblock every 2 hours when exposed to the sun.
_ Deterrence/prevention
Disease flares lead to poor outcome because of reinjury to vital organs. A poor
outcome can be prevented with meticulous medical surveillance and attention to
the chronic nature of the disease. Patient and family education is extremely
important in this regard. Some flares are the result of excessive sun exposure.
These can be avoided using sun protection. (Fluorescent lights may also cause
increased rash in patients with SLE.)
_ Consultations
A rheumatologist should be an integral part of the medical care team supporting the
lupus patient. Other consultations depend on the type of organ involvement.
Consider consultation with a nephrologist for severe end-organ disease.
_ Inpatient Treatment
Inpatient care in patients with systemic lupus erythematosus (SLE) is required for
severe hematologic, nephrologic, neurologic, or psychiatric disease or for
complications from these (eg, severe anemia, renal failure, stroke, seizure),
including the use of intravenous (IV) high-dose corticosteroids or chemotherapy as
required. Hospitalization may also be required for severe hypertension.

Inpatient care is appropriate for the patient with unexplained fever to provide
sepsis evaluation and treatment, as well as to evaluate the patient for disease flare
and to treat him or her accordingly.
- Diet
Dietary restrictions are driven by the patients medical therapy. Most patients
require a course of corticosteroids and should be on a no-added-salt, low-fat,
calcium-sufficient diet. Recognize that patients frequently try nontraditional
medical remedies and food supplements. These remedies should be met with an
open and supportive response. Monitoring nontraditional remedies and food
supplements is important, because they may alter metabolism of more traditional
medications, such as warfarin sodium, or they may have a negative effect. Of note,
L-canavanine in alfalfa sprouts has been implicated in causing lupus, and excess
use should be avoided.

Complications :
Children with lupus may have hematologic abnormalities, including hemolytic
anemia, thrombocytopenia, leukopenia, or lymphopenia. Patients with immune
complex disease in the kidneys may present with nephritis or nephrotic syndrome.
Numerous neurologic abnormalities, from psychosis and seizure to cognitive
disorders to peripheral neuropathies, may also occur. Their exact relationship to the
presence of immune complexes and autoantibodies remains unclear.
Pulmonary disease manifests as pulmonary hemorrhage, fibrosis, or infarct.
Various rashes, gastrointestinal (GI) manifestations, serositis, arthritis,
endocrinopathies , and cardiac abnormalities (eg, valvulitis and carditis) are
observed. No organ is spared from the effects of this multisystem disease.
However, the clinical presentation widely varies. How the clinical manifestations
depend on the underlying specific immunologic disarray in a particular patient
remains to be determined and is the focus of intense study.

Prognosis :
SLE is incurable, but treatable.
In the 1950s, most people diagnosed with SLE lived fewer than five years. Today,
over 90% now survive for more than ten years, and many live relatively a
symptomatically. 80-90% can expect to live a normal lifespan.
Prognosis is typically worse for men and children than for women; however, if
symptoms are present after age 60, the disease tends to run a more benign course.
Early mortality, within 5 years, is due to organ failure or overwhelming infections,
both of which can be altered by early diagnosis and treatment. The mortality risk is
fivefold when compared to the normal population in the late stages, which can be

attributed to cardiovascular disease from accelerated atherosclerosis, the leading

cause of death for people with SLE.
To reduce potential for cardiovascular issues, high blood pressure and high
cholesterol should be prevented or treated aggressively. Steroids should be used at
the lowest dose for the shortest possible period, and other drugs that can reduce
symptoms should be used whenever possible. High serum creatinine, hypertension,
nephrotic syndrome, anemia and hypoalbuminemia are poor prognostic factors.
The ANA is the most sensitive screening test for evaluation, whereas anti-Sm (antiSmith) is the most specific. The dsDNA (double-stranded DNA) antibody is also
fairly specific and often fluctuates with disease activity; as such, the dsDNA titre is
sometimes useful to monitor disease flares or response to treatment.

Epidemiology :
by location and ethnicity. Incidence rates among children younger than age 15
years have been reported to be 0.5-0.6 case per 100,000 persons. Prevalence rates
of 4-250 cases per 100,000 persons have been reported, with greater prevalence in
Native Americans, Asian Americans, Latin Americans, and African Americans. In
one study of adults, the incidence of lupus in African American females was
estimated at 1 in 500. African American children may represent up to 60% of
patients younger than 20 years with lupus. In the pediatric population, just under
60% of cases are seen in patients of African American ethnicity. However, lupus
does occur in persons of every ethnic and racial background.
Prevalence rates are higher in females than in males. A female-to-male ratio of
approximately 4:1 occurs before puberty and after menopause, with a ratio of 8:1
between onset and loss of estrogen cycles.
Approximately 20% of patients with systemic lupus erythematosus initially present
by the second decade of life. Disease onset has been reported as early as the first
year of life. However, SLE remains uncommon in children younger than age 8
years.

Medical Management :
Treatment includes management of acute and chronic disease. Goals of treatment
include preventing progressive loss of organ function, reducing the likelihood of
acute disease, minimizing disease related disabilities, and preventing complications

from therapy. Monitoring is performed to assess disease activity and therapeutic

effectiveness.
_ Pharmacologic Therapy
- Nonsteroidal antiinflammatory drugs (NSAIDs) are used with corticosteroids to
minimize corticosteroid requirements.
- Corticosteroids are used topically for cutaneous manifestations
- IV administration of administration of corticosteroids is an alternative to
traditional high-dose oral use.
- Cutaneous, musculoskeletal, and mild systemic features of cutaneous, SLE are
managed with antimalarial drugs.
- Immunosuppressive agents are generally reserved for the Immunosuppressive
most serious forms of SLE that have not responded to conservative therapies.
The management of secondary thrombocytopenia is usually treatment of the
underlying disease.
Platelet transfusions are used to raise platelet count and stop bleeding or prevent
spontaneous hemorrhage if platelet production is impaired if excessive platelet
destruction is the cause, the patient is treated as indicated for idiopathic
thrombocytopenia purpura. For some patients a splenectomy can be therapeutic,
although it may not be an option for other patients (eg. Patients in whom the
enlarged spleen is due to portal hypertension related to cirrhosis).

Nursing Management :
Interventions focus on preventing injury (eg, use soft toothbrush and electric
razors. Minimize needlestick procedures), stopping or slowing bleeding (eg.
Pressure. Cold), and administering medications and platelets as ordered, as well as
patient teaching.

Patient Education :
The patient and his or her family must have a thorough understanding of systemic
lupus erythematosus (SLE), its potential severity, and the complications of the
disease and its therapy.
Treatment is difficult, especially for adolescent patients. The physician and parents
should expect issues, including depression and noncompliance, to arise. The best
method for deterrence is to thoroughly educate the patient and family through
discussion, support groups, and literature.
Educate all patients with SLE with regard to the serious complications possible
from unplanned pregnancy, poor compliance, recreational drug use, and infection,

including with sexually transmitted diseases (STDs). Poor compliance, in

particular, is a significant prognostic factor.

References :
1- Handbook for Brunner and Suddarth's
Textbook of Medical-Surgical Nursing.
2- http://www.medscape.com/.
3- wikipedia