Systemic Lupus

Erythematosus
(SLE)

Dr Najla Al-Sonboli
Associated Prof.
Paediatrics Department- Sana’a
May 23, 2025
University 1
What is SLE?
A multisystem, autoimmune disorder
that is characterized by the
production of autoantibodies and a
wide variety of clinical and laboratory
manifestations.

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ETIOLOGY
SLE is a multisystem disorder of unknown etiology
characterized by the production of large amounts of
circulating autoantibodies.
This antibody production may be due to loss of T
lymphocyte control on B lymphocyte activity,
leading to hyperactivity of B lymphocytes, which
leads to nonspecific and specific antibody and
autoantibody production.
These antibodies form immune complexes, which
can get trapped in the microvasculature, leading to
inflammation and ischemia.

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EPIDEMIOLOGY
Although SLE is thought to affect women of
child-bearing age, approximately 5% of SLE
presents in childhood, mostly around puberty.
SLE is rare in children younger than 9 years
old.
Although there is a female predominance of this
disease in adulthood and in the teenage years,
there is an equal gender distribution in children.
The overall prevalence of SLE in the pediatric
population is 10 to 25 per 100,000.
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Clinical manifestations:
The most common manifestations of SLE in
children?
Arthritis: 80-90%
Rash/fever: 70%
Renal disease (proteinuria, casts)*: 70%
Serositis: 50%
Hypertension: 50%
Central nervous system disease
(psychosis/seizures): 20-40%
Anemia, leukopenia, thrombocytopenia:
30% each
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 Table 1. Criteria for Diagnosis of
Systemic Lupus Erythematosus*
Physical Signs
– Malar (butterfly) rash
– Discoid lupus
– Photosensitivity
– Oral and nasopharyngeal ulcers
– Nonerosive arthritis (≥2 joints with effusion and
tenderness)
– Pleuritis or pericarditis (serositis)
– Seizures or psychosis in absence of metabolic
toxins or drugs

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Laboratory Data
– Renal Disease (Nephritis)
Proteinuria (>500 mg/24 hr) or
Cellular casts (RBC, granular, or tubular)
– Hematologic Disease
Hemolytic anemia with reticulocytosis or
Leukopenia (<4000 on 2 occasions) or
Lymphopenia (<1500 on 2 occasions) or
Thrombocytopenia (<100,000/mm3)

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Serologic Data
– Positive anti-dsDNA or
– Positive anti-Sm or
– Evidence of presence of antiphospholipid antibodies IgG
or
– IgM anticardiolipin antibodies or
– Lupus anticoagulant or
– False-positive VDRL for >6 mo
– Positive ANA in absence of drugs known to induce lupus
These are the 1997 revised criteria for diagnosing
systemic lupus erythematosus (SLE). A patient must
have 4 of the 11 criteria to establish the diagnosis of
SLE. These criteria may be present at the same or at
different times during the patient's illness.
Additional, less diagnostic manifestations are noted
in Table 2.
ANA, antinuclear antibody; RBC, red blood cell; VDRL, Venereal Disease
Research Laboratory.
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Patients with SLE can present in
an abrupt fashion with fulminant
disease, or in an indolent manner
(Tables 1 and 2). Nonspecific
symptoms are common but can
be quite profound and may
include significant fatigue and
malaise, low-grade fever, and
weight loss.
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 Table 2. Additional Manifestations of
Systemic Lupus Erythematosus
Systemic
– Fever
– Malaise
– Weight loss
– Fatigue
Musculoskeletal
– Myositis, myalgia
– Arthralgia
Cutaneous
– Raynaud phenomenon
– Alopecia
– Urticaria-angioedema
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Neuropsychiatric
– Personality disorders
– Stroke
– Peripheral neuropathy
– Chorea
– Transverse myelitis
– Migraine headaches
– Depression
Cardiopulmonary
– Endocarditis
– Myocarditis
– Pneumonitis

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 Ocular
– Episcleritis
– Retinal cytoid bodies
Gastrointestinal
– Pancreatitis
– Mesenteric arteritis
– Serositis
– Hepatomegaly
– Hepatitis (chronic lupoid)
– Splenomegaly
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Renal
– Nephritis
– Nephrosis
– Uremia
– Hypertension
Reproduction
– Repeat spontaneous abortions
– Neonatal lupus erythematosus
– Congenital heart block

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 LABORATORY AND IMAGING
STUDIES
Testing for SLE is performed for several
reasons:
– to make the diagnosis,
– to determine prognosis, and
– to monitor response to therapy.

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Although a nonspecific test, a positive ANA is found in
more than 97% of patients with SLE, usually at high
titers. Because of its high sensitivity, a negative ANA
has a high negative predictive value for SLE so that it
is unlikely for a patient with a negative ANA to have
SLE.
The presence of antibodies to double-stranded
DNA should raise suspicion for SLE because these
antibodies are present in most patients with SLE and
are found almost exclusively in the disease, as are
antibodies directed against Sm (Smith).
Antibodies to Sm are found in only approximately 30%
of persons with SLE, limiting its clinical utility.
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Antibodies to Ro (SSA) and La (SSB) also can be
found in patients with SLE, but were originally
described in patients with Sjögren syndrome and are
not specific to SLE.
Likewise, patients with SLE can have antibodies
directed against phospholipids, which also can be
seen in other rheumatologic diseases and in primary
antiphospholipid syndrome.
These antibodies lead to an increased risk of arterial
and venous thrombosis and can be detected by the
presence of anticardiolipin antibodies, a false-positive
VDRL test, or a prolonged activated partial
thromboplastin time.
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 Hematologic abnormalities
also are prevalent in patients with SLE. Leukopenia,
primarily manifested as lymphopenia, is common.
Thrombocytopenia and anemia of chronic disease
may be found.
Rarely, patients with SLE develop Coombs-positive
auto-immune hemolytic anemia, which is manifested
by the presence of schistocytes and fragmented cells
on peripheral blood smear.
Excessive antibody production can lead to polyclonal
hypergammopathy, with an elevated globulin fraction
in the serum.

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 Excessive circulating antibodies and
immune complexes also lead to the
consumption of complement proteins, with
low levels of C3 and C4 and decreased
complement function as measured by
CH50.
Effective therapy returns the low
complement levels to normal. This is one
way to monitor therapy except in some
patients with familial deficiency in
complement components, which itself
predisposes to SLE.
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 Urinalysis shows hematuria and proteinuria,
which is crucial in identifying patients with lupus
nephritis.
Serum BUN and creatinine should be obtained
to evaluate renal function. Hypoalbuminemia
and hypoproteinemia may be present.
Elevation of muscle enzymes may be a clue
for the presence of myositis.
Elevated CSF protein and an elevated IgG-to-
albumin ratio when comparing CSF with serum
(IgG index) can indicate antibody production in
the CSF and help diagnose SLE affecting the
CNS.
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Should children with SLE undergo a renal
biopsy?
This is an area of controversy because nearly
all children with SLE will have some evidence
of renal involvement.
Usually clinical disease (e.g., abnormal urine
sediment, proteinuria, renal function changes)
correlates with the severity of renal disease on
biopsy, but this is not always the case.

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Extensive glomerular abnormalities can be
found on biopsy with minimal concurrent
clinical manifestations. For this reason, many
authorities are aggressive with early biopsy.
Three circumstances in particular warrant
biopsy:
– A child with SLE and nephrotic syndrome-to
distinguish membranous glomerulonephritis from
diffuse proliferative glomerulonephritis (which
would warrant more aggressive therapy)
– Failure of high-dose corticosteroids to reverse
deteriorating renal function-to determine the
likelihood of benefit from cytotoxic therapy
– A prerequisite to entry into clinical therapeutic
trials
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 DIFFERENTIAL DIAGNOSIS
Because SLE is a multisystem disease, it can be
difficult to diagnosis early in the disease course.
Suspicion for SLE must be high in patients who
present with diffuse symptoms, particularly in
adolescent girls. Many of the clinical manifestations of
SLE are found in other inflammatory illnesses and
during acute or chronic infection.
Criteria have been developed for the diagnosis of SLE
(see Table 1).
The presence of 4 of 11 of these criteria has 98%
sensitivity
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and 97% specificity for SLE. 23
 TREATMENT
Corticosteroids
– have been the mainstay of treatment for SLE for decades.
– Initial use of pulse methylprednisolone and high-dose oral prednisone
(up to 2 mg/kg) frequently are required to treat SLE, followed by cautious
tapering to minimize recurrence of symptoms.
NSAIDs
– have been used to treat the arthralgias and arthritis associated with SLE.
Hydroxychloroquine
– is used not only for the treatment of lupus skin disease, such as discoid
lupus, but also has been found to be helpful as maintenance therapy in
the disease.
– Patients with SLE who take hydroxychloroquine have been shown to
have longer periods of wellness between flares of disease and
decreased numbers of flares.
For lupus nephritis or cerebritis, corticosteroids and
hydroxychloroquine frequently are not sufficient therapies.
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Cyclophosphamide
– is effective for the worst forms of lupus nephritis,
with significant improvements in outcome and
decreased rates of progression to renal failure.
– Similarly, CNS lupus has been shown to respond to
cyclophosphamide.
azathioprine, methotrexate, or
mycophenolate mofetil
– For patients who are not able to tolerate the
tapering of their corticosteroids, the use of steroid-
sparing agents, such as azathioprine,
methotrexate, or mycophenolate mofetil, may be
indicated.
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 Patients with SLE should be counseled to
wear sun block and stay out of the sun
because the sun has been shown to lead
to flares of the disease.
Because of this prohibition, patients
benefit from supplementation with calcium
and vitamin D to reduce the risk of
osteoporosis that may result from
prolonged cortico-steroid use.

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 COMPLICATIONS
Long-term complications include avascular
necrosis owing to corticosteroid use,
infections, and myocardial infarction.
Adult patients with SLE develop accelerated
atherosclerosis, based not only on
prolonged cortico-steroid use, but also on
the disease.
All patients with SLE should be counseled
regarding their weight and to maintain an
active lifestyle to reduce other cardiac risk
factors.
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 PROGNOSIS
Outcomes for SLE have improved significantly over
the last several decades and depend largely on the
organ systems that are involved.
Survival rates at 10 years are close to 90%; 20-year
survival, however, drops down to approximately 75%.
Worse prognoses are seen in patients with severe
lupus nephritis or cerebritis, with risk of chronic
disability or progression to renal failure.
With current therapy for the disease and the success
of renal transplantation, however, most patients live
well into adulthood.
Most pediatric lupus deaths are the result of infections.
About half of patients with childhood lupus still have
active
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disease as adults. 28
 Thanks for
your attention

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