INTRODUCTION
Systemic lupus erythematosus (SLE) is a chronic
ETIOLOGI
1. Faktor GENETIK
2. Faktor ENDOKRIN
3. Faktor OBAT
4. Faktor INFEKSI
T-Cell dysfunction
B-Cell activation
Abnormal Cytokine production
Bottom line:(the above factorsand other immune
T-Cell Dysfunction
Decreased Th1
activity--> normally
regulate other Tcells
o Decreased IL-2,
TNF-alpha, INFgamma
Increased Th2
activity--> normally
regulate B cell
growth
o IL-4,5,6,10
antigen binds
here
B-Cell Activation
PATOFISIOLOGI
LES timbul sebagai ekspresi klinis suatu
This time...
House is
wrong...
Systemic Lupus
Erythematosus
A chronic inflammatory systemic
autoimmune disease of unknown
etiology characterized by polyclonal
B-cell activation and abnormal
autoantibodies
MANIFESTASI KLINIS
Gejala yang timbul merupakan manifestasi
Kelelahan
90%
Panas lama
80-82%
BB turun
60%
Artritis/Artralgia
90%
Kulit
50-58%
LES
Paru
38%
Hematologi
50%
Jantung
48%
Vaskulitis
Ginjal
50%
SYMPTOMS
SYMPTOMS
PERCENTAGE (%)
95
90
90
81
Skin Rashes
74
Anemia
71
Kidney Involvement
50
45
42
30
Hair loss
27
20
17
12
Systemic Lupus
Erythematosus
butterfly rash
Skin rashes
Finger turns blue
Immunogenetics
Increased Risk for SLE in:
HLA-DR2 (anti-DNA Abs)
HLA-DR3 (anti-Ro Abs)
Null alleles at C2 and C4 loci
SLE may be transmitted in an
autosomal dominant pattern (family
studies)
SLE Genetic
Susceptibility
MHC Related
HLA-DR1, 2, 3, 4
Alleles of HLA-DRB1, IRF5,
and STAT4
C2 - C4 deficiency
TNF- polymorphisms
DIAGNOSIS
Criterion
Definition
DIAGNOSIS
Criterion
Definition
2. Discoid rash: Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic
3. Photosensitivity: Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation
From http://www.rheumatology.org/publications/classification/SLE/1997UpdateOf1982RevisedCriteriaClassificationSLE.asp?aud=pat
Malar
rash
Arthritis (with
swelling)
Arthritis (Jaccouds)
Photosensiti
vity
5-
SLE Pathogenetic
Mechanisms
Immune complex-mediated damage: glomerulonephritis
Direct autoantibody-induced damage: thrombocytopenia
Immune-complex Injury in
SLE
DNA + Anti-DNA = DNA - Anti-DNA
complex
C3
C4
Tissue Injury
SLE:
Anti-DNA,
C3, C4
lupus?
warrants
it!
disease
Procoagulant State
(multifactorial, APS)
Strokes
Premature or Accelerated
Atherosclerosis
PVD
MIs
CV System
Pericarditis 6-45% of patients: low likelihood of tamponade or constrictive
type.
<10% with myocarditis
Libman-Sacks endocarditis
Study data showed that risk of MI was 50x higher in woman with lupus ages 35-44 and
2.5-4x higher in older age groups
Autopsy data shows CAD in 40% of SLE patients as opposed to only 2% of age matched
controls.
Atherosclerotic plaque burden (via carotid intima media thickness measurements and
by coronary calcium scores) is higher in patients with SLE than in controls
Lupus dyslipoproteinemia is low HDL, high TG, normal or only slightly elevated LDL,
increased lipoprotein(a): this appears to correlate with disease activity
Means of prevention focus on risk factor management and inflammation control, but no
clear guidelines are available as of yet.
SLE Heme
Manifestations
Autoimmune hemolytic anemia (AHA)
Autoimmune thrombocytopenia, ITP-like
Leukopenia
Pancytopenia
Lymphopenia
Anti-phospholipid antibodies False
positive
RPRs (neg FTA)
Lymphadenopathy
Rarely, aplastic anemia (from anti-stem
cell antibodies)
CNS Lupus
Seizures - Epilepsy
Strokes with hemiparesis
Coma (lupus cerebritis)
Cranial nerve and peripheral neuropathies
Brain stem/cord lesions
Aseptic meningitis
Transverse myelitis
Psychiatric: memory loss, cognitive
changes
Myasthenia gravis, multiple-sclerosis like
with Raynauds
anticoagulant,
cardioprotective
Cytotoxics: cyclophosphamide (Cytoxan), MTX, mycophenolate mophetil
(CellCept), azathioprine (Imuran)
IVIG: short-lived correction of thrombocytopenia *
Plasmapheresis: not well documented. Used for CAPS
Experimental: LJP394 (B cell tolerogen for anti-DNA Abs), CTLA4Ig
(abatacept), anti-C5 (? efficacy), anti-T and B cell targets (CD40-CD40L,
rituximab (Rituxan), anti-BLYS Rx (lymphostat-B, belimumab), MEDI545, an anti-IFN monoclonal antibody (MedImmune, Inc.), kinase
inhibitors, prolactin inhibitors, etc
Experimental combination Rx: Cytoxan + CTLA4Ig, other combos, etc
Bone marrow approaches: ablative therapy and stem cell transplant
*Gonzalez EB, Truslow W, Miller SB. Intravenous immunoglobulin (IVIG) offers short-term limited benefit in lupus
thrombocytopenia. Arthritis & Rheumatism 36: S228, 1993
Corticosteriods
-Also known as glucocortocoids, cortisone, or just steroids
Anti Inflammatory
- Used to treat inflammation and pain
- Examples include Aspirin, Acetaminophen, and Nonsteroidal anti inflammatory drugs (NSAID) such as
Ibuprofen
Immunosuppressives
-Used to control inflammation and an overactive immune system
-Cylcophosphoamide
-Shown to improve kidney and lung disease
-Methotrexate
-One of the best known treatments for rheumatoid arthritis
-Azathioprine
-Helps to lower steroid dosage and improve liver and
kidney disease
-Obviously there are serious side effects such as reduced ability to
fight off infection
Autoantibodies
ANA: against targets in the nucleus, but only those which have
Mechanism Summary
Defects in clearance of apoptotic cells
Skin disease
Inflammation and breakdown of the dermal-epidermal
junction.
UV exposure can worsen because it promotes apoptosis in
the skin resulting in autoantibody binding and tissue injury
via complement activation or inflammatory cell activation
Anti-Ro antibodies are associated with skin flares
Renal:
A) Proteinuria (>500
mg/24hrs)
B) Cellular casts
Anti-nuclear antibodies
(ANA)
Rim
Nucleolar
Diffuse
Speckled
LE Cell
The LE cell is a
patients experience
renal developments.
Most Dangerous:
Glomerulonephritis
where at least 50% of
the glomeruli have
cellular proliferation
Glomeruli capillary
beds in the kidney that
filter the blood.
Normal
of Glomerulonephritis
is the leading cause of
death among lupus
patients.
Glomerulonephritis
Summary
Lupus = Autoimmunity
Systemic and affects connective tissue