Transcript Definition,Epidemiology,Age at Onset,Causes of SLE,Drugs

This lecture was conducted during the Nephrology Unit Grand
Ground by Medical Student under Nephrology Division under
the supervision and administration of Prof. Jamal Al Wakeel,
Head of Nephrology Unit, Department of Medicine and Dr.
Abdulkareem Al Suwaida, Chairman of Department of
Medicine and Nephrology Consultant. Nephrology Division is
not responsible for the content of the presentation for it is
intended for learning and /or education purpose only.
Presented By:
Dr. Majed Abaalkhail
Medical Student
2009
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Systemic lupus erythematosus is an
autoimmune rheumatic disorder of unknown
cause that typically strikes young women
The word lupus, meaning wolf, derives from
this characteristic rash that was thought to
resemble wolf's markings; erythematosus is
derived from the Latin word for redness
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The damage of lupus occurs when the
immune system produce antibodies that
attack the body's own tissues.
Abnormalities of the immune system also
make people with lupus vulnerable to
infections
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the reported prevalence of systemic
lupus erythematosus (SLE) world wide
is 40 to 50 cases per 100,000.
Due to improved detection of mild
disease, the incidence has nearly tripled
in the last 40 years.
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Sixty-five percent of patients with
SLE have disease onset between the
ages of 16 and 55. Of the remaining
cases, 20 percent present before age
16, and 15 percent after age 55.
The specific cause of SLE is unknown .
 Research suggests that many factors
contribute to the immune dysregulation
observed in SLE .
These factors are :
1) Genetic factors
2) Environmental factors (UV light, stress .. )
3) Hormonal factors ( Estrogen .. )
4) Drugs
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Drug-induced lupus erythematosus is a reversible
condition .
Drug-induced lupus mimics systemic lupus,
however, symptoms of drug-induced lupus generally
disappear once a patient is taken off the medication
which triggered the episode.
There are about 400 medications currently in use that
can cause this condition & most common drugs are
procainamide, quinidine (antiarrhythmic) ,
hydralazine (vasodilator) and isoniazid (anti-TB).
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Lupus disease can be divided according to
symptoms and site of body involved into two
main categories: cutaneous & systemic .
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Cutaneous LE usually provoked by
sunlight
Types: discoid lupus, subacute lupus,
lupus profundus, cutanous lupus
mucinosis &neonatal lupus.
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Discoid lupus:
Is the most common type of cutanous lupus.
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Subacute lupus:
Chracteristics: a non-itchy dry rash appears on
the upper back and chest, often following sun
exposure.
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SLE may begin suddenly or develop slowly over months or
years. Chronic fatigue, unexplained fever, weight loss & loss of
appetite are common systemic complaints.
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Muscle aches.
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Joint pain.
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The most common skin presentation in SLE is
butterfly rash (specific feature).
Features:
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In SLE, deposits of antibodies accumulate in the
glomeruli which causes persistent inflammation of
kidneys called lupus nephritis.
The World Health Organization has divided lupus
nephritis into six classes based on biopsy findings
 Class I is minimal mesangial
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glomerulonepphritis.
Class II is based on a finding of mesangial
proliferative lupus nephritis.
Class III is focal proliferative nephritis.
Class IV is diffuse proliferative nephritis.
Class V is membranous nephritis.
Class VI Glomerulosclerosis.
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Blood disorders can affect up to 85% of patients with
SLE.
These disorders are:
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Anemia: The most common hematological
abnormality in SLE is anemia.
Thrombocytopenia.
Granulocytopenia and Lymphocytopenia: increasing
susceptibility to infections
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Nerve disorders can affect up to 25% of those with
SLE.
CNS Vasculitis is the most serious form of systemic
lupus
Other symptoms include headache, seizures, memory
impairment, cognitive dysfunction ……..
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Inflammation of various parts of heart may
occur as pericarditis, endocarditis or
myocarditis . Chest pain & arrhythmias may
result from these conditions .
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SLE can increase risk of atherosclerosis which can
lead to coronary artery disease.
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Chronic diffuse interstitial lung disease
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pluritis
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SLE can cause other manifestation as
pulmonary hypertention, pleural effusion,
pulmonary hemorrhage (rare fatal
complication).
In 1971
The American College of Rheumatology (ACR)
established a criteria to diagnose SLE witch
consist of 11 items .
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4 of these items are enough to establish a
diagnosis.
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- Items :
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1- Malar rash
2- Discoid rash
3-Photosensetivity
4-Oral ulcer
5-Non- erosive arthritis
6-Pleuritis or pericarditis
7-Renal disorder
8- Seizures or phsychosis
9- Hematolgical disorder
10-Immunological disorder
11- Positive ANA
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NSAIDs (e.g. ibuprofen..) are useful for
patients with mild disease and arthralgia.
Chloroquine and hydroxychloroquine are also
used in mild disease when symptoms cannot
be controlled with NSAIDs, or for cutaneous
disease.
Topical steroids are used for discoid lupus.
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Corticosteroids form the mainstay of treatment,
particularly in moderate to severe disease.
Imuunosuppressives (e.g. Azathioprine,
cyclophosphamide), Usually in combination
with steroids are used for patients with severe
manifestations ( e.g. renal or cerebral disease)
Infections remain a major cause of morbidity and
mortality in patients with SLE throughout the world,
Almost two decades ago, the Lupus Survival Study
Group examined the causes of death of 1103 patients
with SLE. Infections accounted for 33% of the deaths,
whereas active disease for 31%
WHY?
1- leukopenia
2- Drugs
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The Institute of Molecular and Cell Biology
in Strasbourg - France - has discovered a
protein fragment, the P140 peptide, that is
capable of treating lupus-affected mice.
The initial results of phase II studies in patients
with the disease were published on
November 26 2008 on the website of the
journal Arthritis & Rheumatism.
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When treated with the P140 peptide, lupusaffected mice exhibited a lifespan similar to
that of unaffected animals. Their renal disease
was significantly diminished and they
presented with much less severe inflammatory
and joint symptoms.
The phase IIa clinical study was carried out in
two centers in Bulgaria on 20 lupus patients
who received three subcutaneous injections of
the P140 peptide at 15-day intervals.
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It was shown that this peptide did not generate
any adverse effects (side effects) in the patients,
apart from minor redness at the injection site
that rapidly regressed.
The efficacy of P140 was demonstrated by a
reduction in the anti-DNA auto-antibodies.
Immune globulin levels, which are elevated in
lupus patients, were also regulated.
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It was shown in animals that repeated doses of
P140 peptide did not affect their ability to resist
viral infection, unlike immunosuppressants in
general. Thus P140 peptide constitutes the first
potential candidate for the specific treatment of
lupus.
A phase IIb clinical study involving some 200
patients is currently under way in South
America and Europe.