Download SYSTEMIC LUPUS ERYTHEMATOSIS (SLE)

IN THE NAME OF GOD
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SYSTEMIC LUPUS
ERYTHEMATOSIS
(SLE)
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DEFINITION

Autoimmune

Multisystem disease

Autoantibodies and immune complexes
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EPIDEMIOLOGY


Women of child-bearing years (90%)
Most common age at onset: second and third decade

All ages and ethnic groups
Both sexes

Prevalence in US
10-400/100,000

Prevalence in Iran
30/100,000

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PATHOGENESIS
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PATHOGENESIS
Predisposition
Susceptibility Genes
Induction
Autoimmunity
Expansion
Injury
Clinical Disease
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GENETIC BASIS

Twins:
Monozygotic
Dizygotic

57%
5%
Familial aggregation:
First degree relative


12%
HLA: DR2, DR3
C1q, C2, C4
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ENVIRONMENTAL

Ultraviolet B light

Sex hormones
Estrogen
Androgen

Infectious agent

Drug
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Apoptosis
Macrophages
T-cell
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Apoptosis
SM
Ro/ss-a
DNA
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Apoptosis
Macrophages
T-cell
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Apoptosis
B cell
Macrophages
T-cell
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PATHOGENESIS

UV
Flare of SLE in 70% of patients

Infections:
Induce B and T cells
Recognize self Ag
Auto Ab
EBV:
- More common in SLE patients
- Activate B cell
- Amino acid sequences
Mimic some on DNA
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PATHOGENESIS

Female:
Ab responses than male
OCP & HRT:
Estradiol
Bind to
Risk of SLE (1.2-2 fold)
T & B cell
Activation & Survival
Prolonged immune response
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Genetic
Complement
activity
Environmental
Factors
Immune
comlexes
Apoptosis
Phagocytosis
Auto antigen
Apoptotic
Material
Immunogenic
Ag
Auto antibody
DC
T cell
CD4
B cell
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CLINICAL
MANIFESTATION
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CLINICAL MANIFESTATION

ANY ORGAN CAN BE AFFECTED
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SYSTEMIC MANIFESTATION

Fatigue, Malaise, Fever, Anorexia, Weight loss
95%
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MUSCULOSKELETAL

Polyarthritis (95%)
Most patients
Hands, Wrists, Knees
Deformity
10%
Erosion
Rare

Weakness (25%)
Myositis
Glucocorticoid
Antimalaria
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SYSTEMIC MANIFESTATION
Pain persist in a single joint
Ischemic necrosis of bone
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CUTANEOUS
(80%)
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CUTANEOUS

Butterfly rash (50%):
- Most common
- Flare
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CUTANEOUS

Discoid rash (DLE) (20%)
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RENAL

Nephritis (50%):
Most serious manifestation
U/A: any person with suspected SLE
Class III or IV:
- Microscopic hematuria
- Proteinuria (> 500 mg/24h)
- HTN
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HEMATOLOGIC

Anemia (70%)
Chronic disease
Hemolytic

Leukopenia (65%)
Lymphopenia
Infection: rare
Not require therapy

Thrombocytopenia (15%)
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PULMONARY

Pluritis (30%)
- Most common

Interstitial inflammation

Pulmonary hemorrhage
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CARDIAC

Pericarditis (30%)

Myocarditis (10%)

Endocarditis (10%)
Valvular insufficiencies
Libman-Sacks

Ischemia
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VASCULAR

Risk of vascular events
TIA, Strok, MI

Causes:

APS
Embolization
- Carotid plaque
- Libman-Sacks
Vasculitis
Atherosclerosis
7-10 fold
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GASTROINTESTINAL

Peritonitis

Vasculitis
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OCULAR

Sicca

Conjunctivitis

Retinal vasculitis

Optic neuritis
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NERVOUS SYSTEM

Central
Peripheral

Other causes

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ANTIPHOSPHOLIPID SYNDROM


Risk of
- Clotting (arterial or venous)
- Fetal loss
Tests:
- Anticardiolipin
- Lupus anticoagulant
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ANTIPHOSPHOLIPID SYNDROM

High titer of IgG ACL
- Risk of clotting

Diagnosis:
- One clinical
- One test (repeated 12w apart)
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AUTOANTIBODIES

Most patients 3 y or more before symptom
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AUTOANTIBODIES

FANA:
Prevalence: 98%
Best screaming test

Anti-dsDNA:
Prevalence: 70%
Specific (high titer)
Correlate with disease activity
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AUTOANTIBODIES



Anti-Sm:
- Prevalence: 25%
- Specific
- No clinical correlation
Anti-Ro (SS-A):
- Sicca, Neonatal lupus, Nephritis
Antiphospholipid:
- 50%
- Criteria and APS syndrome
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PATHOLOGY

Class I: Mesangial lupus nephritis
- LM: NL
- IF: Mesangial deposit

Class II: Mesangial prolipherative
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PATHOLOGY

Class III: Focal proliferative

Class IV: Diffuse proliferative

Class: V: Membranous

Class: VI: Sclerotic
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DIAGNOSIS
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DIAGNOSIS

Malar rash

Discoid rash

Oral ulcer

Photosensitivity
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DIAGNOSIS

Arthritis:
Nonerosive
≥ 2 or more peripheral joints

Serositis:
Pleuritis or pericarditis

Renal:
Proteinuria > 500 mg or ≥ 3+, or cellular casts
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DIAGNOSIS

Neurologic:
Seizures or psychosis without other causes

Hematologic:
Hemolytic anemia or
Leukopenia (< 4000) or
Lymphopenia (< 1500) or
Thrombocytopenia (< 100,000)
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DIAGNOSIS

Immunologic disorder:
Anti-dsDNA, anti-Sm, antiphospholipid

Antinuclear antibodies:
By immunofluorescence
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DIAGNOSIS

Criteria for classification

≥ 4 criteria

Specificity: 95%
Sensitivity: 75%

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DRUG-INDUCED LUPUS

Milder

Rarely renal or CNS involvement

Drugs: hydralazine, procainamid…

Positive ANA and Anti histone but rarely Anti-dsDNA

Reversible
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TREATMENT
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TREATMENT

No cure

Patients education

Prophylactic measures:
Sunscreen
Low dose aspirin for antiphospholipid Ab positive
Routine immunization
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TREATMENT

Glucocorticoids:
- For almost any manifestation

Immunomodulating agents:
- Antimalaria Fever, Arthritis, Cutaneous
Prevents flare
- Azathioprine
- Mycophenolate mofetile
- Cyclophosphamide
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CORSE




Range from mild to sever diseases
Survival:
- 95% at 5y and 78% at 20y
Causes of death:
- First decade: disease activity, Renal, Infection
- After: Thromboembolic
Critical:
- Nephritis, Cerebritis, Pulmonary hemorrhage,
Hematologic, Carditis
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