SLE

J.Pudji Rahardjo. Sp.PD – kGH

Jakarta
 SLE : Definition
• a chronic inflammatory disease of unknown
cause
• that can affect the skin, joints, kidneys,
lungs, nervous system, serous
membranes and/or other organs of the
body.
• Immunologic abnormalities, especially the
production of a number of antinuclear
antibodies, are another prominent feature of the
disease.
 SLE : Clinical Manifestation
The clinical course :
Variable and
Characterized by periods of remissions
and chronic or acute relapses.
Women, especially in their 20s and 30s,
are affected more frequently than men.
Patients with SLE are subject to myriad
symptoms, complaints, and inflammatory
involvement that can affect virtually every
organ.
 SLE :
The most common pattern is a mixture of
constitutional complaints with
skin,
musculoskeletal,
mild hematologic,
serologic involvement .
Some patients have predominately
hematologic, renal, or central nervous system
manifestations.
The pattern that dominates during the first few
years of illness tends to prevail subsequently
 SLE : Diagnosis
Straightforward in a patient who presents
with several compatible clinical features
and has supportive laboratory studies.
Example is a young woman who
presents with complaints of fatigue,
arthralgia, and pleuritic chest pain,
who is found to have hypertension, a
malar rash, a pleural friction rub,
several tender and swollen joints, and
mild peripheral edema.
.
 SLE : Diagnosis
Straightforward in a patient who presents
with several compatible clinical features
and has supportive laboratory studies.
Laboratory testing may reveal leukopenia,
anemia, an elevated serum creatinine,
hypoalbuminemia, proteinuria, an
active urinary sediment,
hypocomplementemia, a positive
Coombs test, and positive tests for
antinuclear antibodies, including those
to double stranded DNA and the Smith
(Sm) antigen.
 SLE : Diagnosis
Straightforward in a patient who presents
with several compatible clinical features
and has supportive laboratory studies.
Laboratory testing may reveal leukopenia,
anemia, an elevated serum creatinine,
hypoalbuminemia, proteinuria, an
active urinary sediment,
hypocomplementemia, a positive
Coombs test, and positive tests for
antinuclear antibodies, including those
to double stranded DNA and the Smith
(Sm) antigen.
 SLE : Diagnosis
• Straightforward in a patient who presents
with several compatible clinical features
and has supportive laboratory studies..
SLE can also cause isolated
cytopenias or single organ
involvement (eg, nephritis or
pericarditis), or may first be
manifested by an incidental laboratory
finding, such as a biologic false
positive test for syphilis.
Such patients may subsequently develop the
characteristic multisystem features of SLE
over a period of months or years.
 Presenting clinical manifestations
Usually SLE begins with one or several of the following features :

• Unexplained nonspecific symptoms such as fever, fatigue, or weight

loss.
• Photosensitive rash
• Arthralgia or arthritis
• Raynaud phenomenon
• Serositis (pleuritis, pericarditis, peritonitis)
• Nephritis or nephrotic syndrome
• Neurologic symptoms such as seizures or psychosis
• Alopecia
• Phlebitis
• Recurrent miscarriage
• Anemia

• SLE should also be suspected in young women presenting with

purpura, easy bruising, diffuse adenopathy, hepatosplenomegaly,
peripheral neuropathy, endocarditis, myocarditis, interstitial
pneumonitis, or aseptic meningitis. A positive Coombs test,
hypocomplementemia, and immune deposits at the dermal-epidermal
junction on skin biopsy are other findings suggestive of lupus.
 Laboratory testing
Laboratory tests that may provide diagnostically useful information when SLE
is suspected include:
• Complete blood count and differential
• Comprehensive metabolic profile
• Creatine kinase
• Erythrocyte sedimentation rate and/or C reactive protein
• Urinalysis
• 24-hour urine collection for calculation of creatinine clearance
• and quantitation of proteinuria or protein/creatinine ratios

Autoantibody testing is also indicated (see 'Autoantibodies' below). Those

autoantibodies that are routinely assayed are:
• Antinuclear antibodies (ANA)
• Antiphospholipid antibodies
• Antibodies to double stranded DNA
• Anti-Smith (Sm) antibodies

Measurement of serum complement levels C3 and C4 may also be helpful,

since hypocomplementemia is a frequent finding in active SLE.
 Laboratory testing
Laboratory tests that may provide diagnostically useful information
when SLE is suspected include:
• Complete blood count and differential
• Comprehensive metabolic profile
• Creatine kinase
• Erythrocyte sedimentation rate and/or C reactive protein
• Urinalysis
• 24-hour urine collection for calculation of creatinine clearance
• and quantitation of proteinuria or protein/creatinine ratios

Autoantibody testing is also indicated (see 'Autoantibodies' below).

Those autoantibodies that are routinely assayed are:
• Antinuclear antibodies (ANA)
• Antiphospholipid antibodies
• Antibodies to double stranded DNA
• Anti-Smith (Sm) antibodies

Measurement of serum complement levels C3 and C4 may also be helpful,

since hypocomplementemia is a frequent finding in active SLE.
 Imaging
Diagnostic imaging may be valuable
but is not routinely obtained unless
indicated by the presence of
symptoms, clinical findings, or
laboratory abnormalities. Examples
include:
– Plain radiographs of involved joints
– Renal ultrasonography to assess kidney
size and rule out urinary tract
obstruction when there is evidence of
renal impairment
– Chest radiography
 Imaging
Diagnostic imaging may be valuable but is not
routinely obtained unless indicated by the
presence of symptoms, clinical findings, or
laboratory abnormalities.
Examples include:
– Echocardiography (eg, for suspected pericardial
involvement, to assess for a source of emboli, or
noninvasive estimation of pulmonary artery pressure)
– Computed tomography (CT) (eg, for abdominal pain,
suspected pancreatitis)
– Magnetic resonance imaging (eg, for focal neurologic
deficits or cognitive dysfunction)
– Contrast angiography may be valuable if vasculitis
affecting medium sized arteries is suspected (eg,
mesenteric or limb-threatening ischemia)
 Biopsy & Other tests

• Biopsy of an involved organ (eg, skin

or kidney) is necessary in some cases.
There are typical histologic findings in
various organs in SLE to the particular
sites of involvement, such as the
kidney.
 Biopsy & Other tests
• Other tests that may be necessary are
typically dictated by the clinical presentation
and associated differential diagnostic
possibilities.
Examples include:
– Electrocardiography in the assessment of chest
pain that may be due to pericarditis
– Tests to assess for pulmonary embolism in a
patient with pleuritic chest pain and dyspnea
– Diffusing capacity for carbon monoxide (DLCO) to
assess for suspected pulmonary hemorrhage and
estimate the severity of interstitial pneumonitis
 Diagnostic criteria
• A useful approach to the detection of SLE and in
differentiating it from other systemic disorders
has been the use of a questionnaire.
• If three or more questions are answered
positively, SLE is a possibility and an ANA test is
indicated.
• Testing for antinuclear antibodies has replaced
looking for evidence of phagocytosis of nuclear
material (LE cells) in a blood smear, but LE cells
may still be noted incidentally in body fluids such
as pleural or pericardial effusions.
Questionnaire for the diagnosis of systemic lupus
erythematosus
• Have you ever had arthritis or rheumatism for more than 3 months?
• Do your fingers become pale, numb, or uncomfortable in the cold?
• Have you had any sores in your mouth for more than 2 weeks?
• Have you been told that you have low blood counts (anemia, low
WBC count, or low platelet count)?
• Have you ever had a prominent rash on your cheeks for more than
1 month?
• Does your skin break out after you have been in the sun (not
sunburn)?
• Has it ever been painful to take a deep breath for more than a few
days (pleurisy)?
• Have you ever been told that you have protein in your urine?
• Have you ever had rapid loss of lots of hair?
• Have you ever had a seizure, convulsion, or fit?
 ARA Criteria for diagnosis of SLE
Criterion Definition

Malar rash Fixed erythema, flat or raised, over the malar eminences,
tending to spare the nasolabial folds
Discoid rash Erythematosus raised patches with adherent keratotic
scaling and follicular plugging; atrophic scarring may
occur in older lesions
Photosensitivity Skin rash as a result of unusual reaction to sunlight, by
patient history or physician observation
Oral ulcers Oral or nasopharyngeal ulceration, usually painless,
observed by a physician
Arthritis Nonerosive arthritis involving 2 or more peripheral joints,
characterized by tenderness, swelling, or effusion
Serositis Pleuritis - convincing history of pleuritic pain or rub heard by
a physician or evidence of pleural effusion OR
Pericarditis - documented by EKG, rub or evidence of
pericardial effusion
Renal disorder Persistent proteinuria greater than 0.5 grams per day or
greater than 3+ if quantitation not performed OR
Cellular casts - may be red cell, hemoglobin, granular, tubular, or
mixed
 ARA Criteria for diagnosis of SLE
Criterion Definition

Neurologic disorder Seizures OR psychosis - in the absence of offending

drugs or known metabolic derangements (uremia,
ketoacidosis, or electrolyte imbalance)
Hematologic disorder Hemolytic anemia - with reticulocytosis OR
Leukopenia - less than 4,000/mm3 total on two or more
occasions OR
Lymphopenia - less than 1,500/mm3 on two or more
occasions OR
Thrombocytopenia - less than 100,000/mm3 in the absence
of offending drugs
Immunologic disorders Positive antiphospholipid antibody OR
Anti-DNA - antibody to native DNA in abnormal titer OR
Anti-Sm - presence of antibody to Sm nuclear antigen OR
False positive serologic test for syphilis known to be
positive for at least six months and confirmed by
Treponema pallidum immobilization or fluorescent
treponemal antibody absorption test
Antinuclear antibody An abnormal titer of antinuclear antibody by
immunofluorescence or an equivalent assay at any
point in time and in the absence of drugs known to
be associated with "drug-induced lupus" syndrome
 Diagnostic criteria
• Most physicians rely on diagnostic
criteria for lupus that were developed
by the American Rheumatism
Association (ARA, now the American
College of Rheumatology or ACR)
• These criteria were developed for the
classification of SLE patients when SLE
was compared to other rheumatic
diseases for study purposes.
 Diagnostic criteria
• Whether these criteria apply to other
populations has not been
established, although they have been
used to demonstrate that the
frequency of SLE is higher among
Afro-Americans, Afro-Caribbeans,
Anglo-Asians, and American-
Hispanics than in Caucasians
• SLE is virtually nonexistent among
Blacks in Africa
 Diagnostic criteria
• The diagnosis of SLE is made if four or
more of the manifestations are present,
either serially or simultaneously, during
any interval of observations.
• A positive LE cell test, used in the older
criteria, has been replaced by the
presence antiphospholipid antibodies.
• When tested against other rheumatic
diseases, these criteria have a sensitivity
and specificity of approximately 96
percent.
 Diagnostic criteria
• Using the analogy of the ACR criteria for the diagnosis of
rheumatoid arthritis, suggest that patients be classified as
follows:
– Classical SLE — many criteria
– Definite SLE — four or more criteria
– Undifferentiated connective tissue disease

• Undifferentiated connective tissue disease (UCTD) is

defined as a patient with a positive serology and evidence of
inflammation on examination who does not meet the ACR
criteria for SLE any other autoimmune disorder.

• Patients with UCTD need to be followed carefully and

encouraged to report new symptoms and to have periodic
laboratory testing to assess for the emergence of new
clinical features or laboratory findings.
 Autoantibodies
• The ANA test is the best diagnostic test for
SLE and should be performed whenever SLE
is suspected
• The ANA is positive in significant titer
(usually 1:160 or higher) in virtually all
patients with SLE.
• The probability of having SLE in a population
at variable risk for lupus is less than 0.14
percent if the ANA test is negative.
 Autoantibodies
• Antinuclear antibodies are also
present, usually in lower titer, in a
variety of other disorders ::
– Sjögren's syndrome — 68 percent
– Scleroderma — 40 to 75 percent
(especially with a speckled-pattern of
ANAs)
– Juvenile rheumatoid arthritis — 16 percent
– Rheumatoid arthritis — 25 to 50 percent
(especially with a diffuse pattern of ANAs)
 Autoantibodies
• dsDNA and Sm antibodies
– There are two autoantibodies that are highly specific
for SLE: anti-double-stranded DNA (dsDNA)
antibodies; and anti-Sm antibodies .
– The sensitivity is much lower at about 75 and 25
percent, respectively.
– One study, for example, evaluated seven commercial
ELISA assays for anti-dsDNA antibodies; the
following results were obtained [29]:
• Sensitivity — 66 to 95 percent
• Specificity — 75 to 100 percent
• Predictive value — 89 to 100 percent
 DIFFERENTIAL DIAGNOSIS
• Given the protean manifestations of SLE, the
differential diagnosis is correspondingly broad:
– Systemic symptoms causes of chronic fatigue and weight
loss should be considered.
– Polyarthritis/polyarthralgia
– Renal disease
– Other causes of impaired renal function
– Cutaneous lesions
– Mucosal lesions
– Abdominal pain
– Liver disease
– Lung disease
– Cardiovascular disease
– Central nervous system disease
– Ophthalmologic disease
– Hematologic abnormalities
– Lymphadenopathy
 SLE : PROGNOSIS
• Systemic lupus erythematosus (SLE) is a
chronic, occasionally life threatening,
multisystem disorder.
• Patients suffer from a wide array of symptoms
and have a variable prognosis that depends
upon the severity and type of organ
involvement.
• Due to the uncertain course, effective treatment
requires ongoing patient-doctor communication
to correctly interpret laboratory tests, alleviate
symptoms, prevent and treat relapses, and
lessen side effects related to drug therapy.
 DETERMINATION OF DISEASE ACTIVITY AND
SEVERITY
• An effective therapeutic regimen first
requires the accurate determination of
both disease activity and severity
• Disease activity usually refers to the
degree of inflammation, while severity
implies that organ function and perhaps
its underlying structure is quantitatively
impaired.
• The degree of organ dysfunction has
been referred to as the "damage index".
 DETERMINATION OF DISEASE ACTIVITY AND
SEVERITY
• The presence of severe organ dysfunction
does not necessarily imply ongoing
inflammation. As an example, marked
proteinuria and a decreasing glomerular
filtration rate may result from either active
inflammation or inactive scarring.
• The ability to differentiate between these
two possibilities is extremely important,
since immunosuppressive therapy is not
indicated in the latter setting.
 Clinically useful markers of activity
• Disease activity is assessed using a combination of the clinical
history, physical examination, organ specific functional tests, and
serologic studies
Examples include:
– Active SLE (particularly lupus nephritis) is often preceded by a rise in
IgG anti-double-stranded DNA titers, a fall in complement levels
(especially CH50, C3 and C4), and an elevation in complement split and
activation products.
– Persistently low serum levels of complement C1q are associated with
continued activity of proliferative glomerulonephritis].
– Falling levels of anti-DNA antibodies may occur in association with
active disease
– Increases in the erythrocyte sedimentation rate (ESR) and the serum C-
reactive protein (CRP) concentration are also commonly seen with in
this setting], as well as in association with a broad range of clinical
features, activity, and organ damage in one study [26], but only with
activity (especially constitutional, eye, pulmonary, gastrointestinal, and
neurologic), but not with an index of organ damage.
– There are conflicting data on the diagnostic value of a marked
elevation of CRP in distinguishing active lupus from infection, but a
markedly elevated level of CRP in a patient with SLE should raise the
suspicion for infection.
 Clinically useful markers of activity
• Disease activity is assessed using a combination of the
clinical history, physical examination, organ specific
functional tests, and serologic studies

• However, not all patients with these serologic markers have

active disease and these markers do not necessarily predict
disease exacerbation.
 Frequency of laboratory testing
• Monitoring laboratory tests are tailored to each patient, in
general, patients with more active disease are monitored
more frequently, while those with inactive disease
require less frequent monitoring.
As examples:
– A patient with active lupus nephritis might have a battery of
tests done once weekly.
– For someone with a reduction in glomerular filtration rate
whose disease is stable and who is free of proteinuria,
testing every two to three months may be appropriate.
– A patient with previously active nephritis, a normal
glomerular filtration rate and no proteinuria, whose SLE is
otherwise quiescent, may be tested every four to six
months.
– Someone with no history of renal involvement and
quiescent disease may be retested every 6 to 12 months
The following laboratory tests are suggested for monitoring
in a patient with a previous history of renal involvement
who is currently free of proteinuria and who has a normal
creatinine clearance.

• Complete blood count

• Erythrocyte sedimentation rate
• C-reactive protein
• Urinalysis with examination of urinary sediment
• Spot (untimed) urine protein and creatinine
• Serum creatinine and estimated glomerular filtration rate
(eGFR)
• Serum albumin
• Anti-dsDNA
• Complement (CH50 or C3 and C4)

For patients without a history of lupus nephritis, the spot

(untimed) urine protein and creatinine and serum albumin are
unnecessary.
 GENERAL TREATMENT
CONSIDERATIONS
• Although organ involvement requires specific
drug therapy, a number of general issues are
applicable to every patient with SLE.

• Sun protection — Avoid exposure to direct or

reflected sunlight and other sources of ultraviolet
light (eg, fluorescent and halogen lights). Use
sunscreens, preferably those that block both UV-
A and UV-B, with a minimum skin protection
factor (SPF) of 30.
 GENERAL TREATMENT
CONSIDERATIONS
• Diet and nutrition — Limited data exist concerning the effect
of dietary modification in SLE. Of two studies performed by
one group of investigators, the largest trial randomly
assigned 60 patients to either receive 1.8 grams of
eicosapentanoic acid (EPA) and 1.2 grams of
docosahexanoic acid (DHA) or placebo, daily, for 24 weeks.
Those on fish oil had a significantly greater reduction in an
index of disease activity (SLAM-R) and improvement in
endothelial function as assessed by flow-mediated arterial
dilation than did the placebo group. These findings await
independent confirmation: at present, we do not recommend
fish oil supplements in the treatment of SLE.

• A conservative approach is to recommend a balanced diet

consisting of carbohydrates, proteins, and fats. However,
the diet should be modified based upon disease activity and
the response to therapy
 GENERAL TREATMENT
CONSIDERATIONS
• Vitamins are rarely needed when patients eat a balanced
diet. However, a daily multivitamin should be taken by
patients who are not able to obtain an adequate diet or
who are dieting to lose weight.
• The majority of patients with SLE have low serum levels
of 25-hydroxyvitamin D (calcidiol) [49], probably due at
least in part to avoidance of sun exposure. Patients with
low vitamin D levels should be treated with supplemental
Vitamin D.
• Patients on long-term glucocorticoids and
postmenopausal women should ingest 800 units of
vitamin D plus 1500 mg of calcium per day and/or a
bisphosphonate to minimize the degree of bone loss.

• Herbs are of unproven benefit, and may cause harm.

 GENERAL TREATMENT CONSIDERATIONS
• Exercise — Inactivity produced by acute illness causes a rapid
loss of muscle mass and stamina resulting in a sense of
fatigue. This can usually be treated with graded exercise. In
selected refractory cases, relief can be obtained with
antimalarial drugs.

• Smoking cessation — Cigarette smoking may increase the risk

of developing SLE, and smokers in general have more active
disease. Patients should be counseled not to smoke, or to quit
smoking and provided with help to do so.

• Immunizations — It had been previously thought that

immunization could exacerbate SLE. However, influenza
vaccine and pneumococcal vaccines also safe but resultant
antibody titers are somewhat less in patients with SLE than in
controls. Use of glucocorticoids, such as prednisone, or other
immunosuppressive agents may contribute to the blunted
antibody response.
 GENERAL TREATMENT CONSIDERATIONS
• In contrast, it is inadvisable to immunize potentially
immunosuppressed patients (including those treated with
glucocorticoids alone at doses equivalent to ≥20 mg/day
of prednisone for more than two weeks) with live
vaccines (eg, measles, mumps, rubella, polio, varicella,
and vaccinia [smallpox])

• While the issue of efficacy of vaccination with hepatitis B

vaccine has not been completely resolved, the risks
posed by HepB vaccine to patients with SLE must at
most be very small].
 GENERAL TREATMENT
CONSIDERATIONS
• Radiation therapy — Anecdotal reports of increased toxicity following therapeutic
ionizing radiation have made radiation oncologists wary of treating patients with SLE
and other collagen vascular disorders [59]. Patients with scleroderma may be at
greater risk. However, if needed, radiation therapy may be used in patients with SLE
to treat malignant disease. Two observational series have included 19 patients with
SLE among those with "collagen vascular diseases" receiving radiation therapy for
cancer [60,61]. No unusually severe local reactions in the skin or subcutaneous
tissues in the radiation portal were noted in those with lupus. In contrast, in a study of
17 patients with SLE, four had a grade 3 or higher toxicity at 5 to 10 years, especially
in patients with more severe disease, and more organ involvement [62]. Other studies
[63] and a review [64] arrive at similar conclusions: that radiation therapy can
probably be given to most patients with SLE, except for those with severe multi-organ
disease, to whom radiation therapy should be used with caution if at all.

• Avoidance of specific medications — Some data suggest that sulfonamide-containing

antibiotics (eg, sulfadiazine, trimethoprim-sulfamethoxazole, sulfisoxazole) and
penicillin (but not the semisynthetic penicillins) may cause exacerbations and should
therefore be avoided [65]. This impression with regard to sulfa-containing agents was
supported by the following:

• • A case-control study of 145 patients with SLE and 104 controls; adverse reactions
to sulfonamide-containing antibiotics were more than twice as frequent in those with
SLE (52 versus 19 percent) [66].
 GENERAL TREATMENT
CONSIDERATIONS
• Radiation therapy — Anecdotal reports of increased toxicity
following therapeutic ionizing radiation have made radiation
oncologists wary of treating patients with SLE and other
collagen vascular disorders. Patients with scleroderma may be
at greater risk. However, if needed, radiation therapy may be
used in patients with SLE to treat malignant disease. Two
observational series have included 19 patients with SLE among
those with "collagen vascular diseases" receiving radiation
therapy for cancer. No unusually severe local reactions in the
skin or subcutaneous tissues in the radiation portal were noted
in those with lupus. In contrast, in a study of 17 patients with
SLE, four had a grade 3 or higher toxicity at 5 to 10 years,
especially in patients with more severe disease, and more
organ involvement. Other studies and a review arrive at similar
conclusions: that radiation therapy can probably be given to
most patients with SLE, except for those with severe multi-
organ disease, to whom radiation therapy should be used with
caution if at all.
 GENERAL TREATMENT
CONSIDERATIONS
• Avoidance of specific medications — Some data suggest that
sulfonamide-containing antibiotics (eg, sulfadiazine,
trimethoprim-sulfamethoxazole, sulfisoxazole) and penicillin
(but not the semisynthetic penicillins) may cause exacerbations
and should therefore be avoided. This impression with regard
to sulfa-containing agents was supported by the following:
– A case-control study of 145 patients with SLE and 104
controls; adverse reactions to sulfonamide-containing
antibiotics were more than twice as frequent in those with
SLE (52 versus 19 percent).
– A study of 417 patients with SLE, among whom 114 had a
history of sulfonamide allergy.

• In contrast, medications that cause drug-induced lupus, such

as procainamide and hydralazine, do not cause exacerbations
of idiopathic SLE. This observation is a presumed reflection of
the pathogenetic differences between the two disorders
 GENERAL TREATMENT
CONSIDERATIONS
• Pregnancy and contraception — Pregnancy should be
avoided during active disease (especially with
significant organ impairment) due to the high risk of
miscarriage and exacerbation of SLE. Women with SLE
should be counseled not to become pregnant until the
disease has been quiescent for at least six months.

• Pregnant patients with active lupus are generally

managed with glucocorticoids. Other drugs used during
pregnancy include nonsteroidal antiinflammatory drugs
and hydroxychloroquine (probably safe).
Cyclophosphamide and methotrexate are
contraindicated, while azathioprine can be cautiously
used.
 GENERAL TREATMENT
CONSIDERATIONS
• Oral contraceptives containing high dose estrogens can
cause exacerbations of SLE. However, this complication
rarely occurs with the current use of low-dose estrogen
or progesterone containing compounds. Patients with
migraine headaches, Raynaud phenomenon, a history
of phlebitis, or antiphospholipid antibodies probably
should not be treated with oral contraceptives.
Hormone replacement therapy in postmenopausal
women may be associated with a modest increase in
the rate of flares, and decisions about use of estrogen
for postmenopausal symptoms must be carefully
considered weighing the potential benefits against risks
of thrombotic events, breast and uterine cancer.
 TREATMENT OF SPECIFIC ORGAN
INVOLVEMENT —
• A number of medications are commonly used
in the treatment of SLE, including nonsteroidal
antiinflammatory drugs (NSAIDs), antimalarials
(primarily hydroxychloroquine),
glucocorticoids, and immunosuppressive
agents (including cyclophosphamide,
methotrexate, azathioprine, and
mycophenolate).
• Patient compliance with recommended
treatment is, as expected, associated with
better outcomes than non-compliance.
 TREATMENT OF SPECIFIC ORGAN
INVOLVEMENT —
• Drugs which are preferred in selected clinical settings.
– Topical therapies are often useful for local
problems and reduce the risk of side effects that
are associated with systemic use of NSAIDs,
glucocorticoids, or immunosuppressants such as
tacrolimus (Protopic®).
– NSAIDs are generally effective for
musculoskeletal complaints and mild serositis.
Cyclooxygenase (COX)-2 selective inhibitors may
also be effective in such patients. Of the available
COX-2 inhibitors, celecoxib contains a
benzenesulfonamide moiety and should be used
with caution in those patients with a history of
allergy to sulfonamide containing antibiotics.
However, celecoxib has been used in SLE
patients, even those with "sulfa" allergy, without
precipitating any allergic response.
 TREATMENT OF SPECIFIC ORGAN
INVOLVEMENT —
• Antimalarials ae most useful for skin
manifestations and for musculoskeletal
complaints that do not adequately respond to
NSAIDs.
• In addition, in long-term studies the use of
antimalarials, such as hydroxychloroquine,
prevented major damage to the kidneys and
central nervous system.
• Their use may also reduce the risk of disease
flares; though this is less clear for renal and
central nervous system manifestations ;
antimalarials are not the drugs of choice for
disease in these organ systems.
 TREATMENT OF SPECIFIC ORGAN
INVOLVEMENT —
• Systemic glucocorticoids (eg, high doses
of 1 to 2 mg/kg/day of prednisone or
equivalent or as intermittent intravenous
"pulses" of methylprednisolone) used
alone or in combination with
immunosuppressive agents are generally
reserved for patients with significant
organ involvement, particularly renal and
central nervous system disease. There
are a paucity of data to support the use of
intravenous "pulse" versus daily oral
glucocorticoids.
 TREATMENT OF SPECIFIC ORGAN
INVOLVEMENT —
• Immunosuppressive agents such as
mycophenolate or cyclophosphamide are given
with glucocorticoids to patients with more than
mild lupus nephritis, and cyclophosphamide to
those with alveolar hemorrhage, systemic
vasculitis, and to most patients with significant
central nervous system involvement.
• Lower doses of glucocorticoids (eg, ≤10 mg/day
of prednisone) may be used for symptomatic
relief of severe arthralgia, arthritis, or serositis
while awaiting a therapeutic effect from other
medications.
 TREATMENT OF SPECIFIC ORGAN
INVOLVEMENT —
• Treatment with prednisone as soon as a
significant rise in anti-dsDNA occurs prevented
relapses in most cases in a study of 156
patients. As noted above, however, we follow
such patients closely but do not treat titers in the
absence of clinical evidence of active disease.

• Treatment with immunosuppressive medications

other than glucocorticoids (eg, methotrexate,
cyclophosphamide, azathioprine,
mycophenolate, or rituximab) is generally
reserved for patients with significant organ
involvement, and/or patients who have had an
inadequate response to glucocorticoids.
 RESISTANT DISEASE AND EXPERIMENTAL
THERAPY

• Patients with severe organ involvement

who are resistant to
cyclophosphamide therapy generally
do poorly.
• The optimal approach to such patients
is uncertain.
 PROGNOSIS
• SLE can run a varied clinical course, ranging
from a relatively benign illness to a rapidly
progressive disease with fulminant organ
failure and death. Most patients have a
relapsing and remitting course, which may be
associated with the use of high dose steroids
during the treatment of severe flares.
 PROGNOSIS
• Patient survival — The five-year survival rate in SLE
has dramatically increased over the last several decades
from approximately 40 percent in the 1950s to more than 90
percent in studies beginning after 1980, a trend that has
continued into the early 21st century.
• The likelihood of survival can be ranked on the basis of
organ involvement (skin and musculoskeletal best, central
nervous system and kidney worst) and on the number of
American College of Rheumatology criteria for SLE. Older
age, male sex, poverty, and a low complement may also be
poor prognostic factors, as was noted in a cohort of North
American patients. However, increasing age was not a
predictor of an increased mortality rate in one Chinese
cohort of 442 patients when compared to a age-adjusted
population mortality rate. Measures of disease activity and
accumulated organ damage may also be predictive or
increased mortality while use of antimalarial drugs may
reduce mortality rates.
 PROGNOSIS
• The improvement in patient survival is probably due to
multiple factors. These include increased disease
recognition with more sensitive diagnostic tests , earlier
diagnosis or treatment, the inclusion of milder cases, and
increasingly judicious therapy and prompt treatment of
complications .

• In a 2002 report from the Centers for Disease Control in

the United States, deaths due to SLE varied among
different population groups. As examples, the proportion
of deaths due to SLE was more than five times higher in
women than men, and more than three times higher in
black compared to white women. More than one-third of
deaths due to lupus occurred in people aged 15 to 44
years.
 Causes of death
• The major cause of death in the first few years of illness is active
disease (eg, CNS, renal, or cardiovascular disease) or infection due
to immunosuppression, while late deaths are either caused by the
illness (eg, end-stage renal disease), treatment complications
(including infection and coronary disease), non-Hodgkin lymphoma,
and lung cancer.
– One study evaluated the causes of death in 408 patients with SLE
followed over a mean period of 11 years; 144 (35 percent) died
[133]. The major causes of death were active lupus (34 percent),
infection (22 percent), cardiovascular disease (16 percent), and
cancer (6 percent). Deaths that resulted directly from SLE and
infection were common among younger patients; the risk of death
directly due to SLE was highest in the first three years after
diagnosis.
• • Another prospective study followed 1000 patients for 10 years
[120]. The most frequent causes of death were active SLE (26
percent), infection (25 percent), and thromboses (26 percent) [120].

• • In a cohort of 4747 Swedish patients who were diagnosed with

SLE between 1964 and 1995, the proportion of deaths due to
cardiovascular events, SLE, and malignant disease were 42
 Causes of death
• Causes of death — The major cause of death in the first few years of illness is active disease (eg, CNS, renal, or
cardiovascular disease) or infection due to immunosuppression, while late deaths are either caused by the illness
(eg, end-stage renal disease), treatment complications (including infection and coronary disease), non-Hodgkin
lymphoma, and lung cancer [126,128-132]. The frequency of the different causes of death can be illustrated by the
following observations:

• • The largest study to date included survival data and causes of death in a total of 9547 patients who were
followed for an average of 8.1 years [132]. Standardized mortality rates (SMR) of SLE patient to expected rates for
a age and sex adjusted population were noted for circulatory disease (SMR 1.7), especially heart disease (SMR
1.7), non-Hodgkin lymphoma (SMR 2.8), lung cancer (SMR 19.4), infections (SMR 9.0), especially pneumonia
(SMR 7.2), and renal disease (SMR 4.3). Those at particular high risk for mortality were younger, female, and
black, with a disease duration of less than one year.

• • One study evaluated the causes of death in 408 patients with SLE followed over a mean period of 11 years; 144
(35 percent) died [133]. The major causes of death were active lupus (34 percent), infection (22 percent),
cardiovascular disease (16 percent), and cancer (6 percent). Deaths that resulted directly from SLE and infection
were common among younger patients; the risk of death directly due to SLE was highest in the first three years
after diagnosis.

• • Another prospective study followed 1000 patients for 10 years [120]. The most frequent causes of death were
active SLE (26 percent), infection (25 percent), and thromboses (26 percent) [120].

• • In a cohort of 4747 Swedish patients who were diagnosed with SLE between 1964 and 1995, the proportion of
deaths due to cardiovascular events, SLE, and malignant disease were 42 percent, 21 percent, and 12 percent
respectively [134].

• Serious infection is most often due to immunosuppressive therapy. (See "Secondary immune deficiency due to
miscellaneous causes", section on 'Systemic lupus erythematosus'.) Patients at particular risk are those treated
with both glucocorticoids and cyclophosphamide, especially if the white blood cell count is less than 3000/µL
and/or high-dose steroids are given [135,136]. Lymphopenia (<1000/µL) at presentation, may be an independent
risk factor [137]. (See "General toxicity of cyclophosphamide and chlorambucil in inflammatory diseases" and
"Major side effects of systemic glucocorticoids".)

• Premature coronary artery disease is being increasingly recognized as a cause of late mortality. (See "Coronary
heart disease in systemic lupus erythematosus".)