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IN THE NAME OF GOD

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SYSTEMIC SYSTEMIC LUPUS LUPUS

ERYTHEMATOSIERYTHEMATOSISS

(SLE)(SLE)

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DEFINITIONDEFINITION Autoimmune Autoimmune

Multisystem diseaseMultisystem disease

Autoantibodies and immune Autoantibodies and immune complexes complexes

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EPIDEMIOLOGYEPIDEMIOLOGY

Women of child-bearing years (90%)Women of child-bearing years (90%) Most common age at onset: second and Most common age at onset: second and

third decade third decade

All ages and ethnic groupsAll ages and ethnic groups Both sexes Both sexes

Prevalence in US 10-400/100,000 Prevalence in US 10-400/100,000

Prevalence in Iran 30/100,000Prevalence in Iran 30/100,000

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PATHOGENESIPATHOGENESISS

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PATHOGENESISPATHOGENESIS

PredispositionSusceptibility Genes

InductionAutoimmunity

InjuryClinical Disease

Expansion

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GENETIC BASISGENETIC BASIS

Twins:Twins:Monozygotic 57%Monozygotic 57%

Dizygotic 5%Dizygotic 5%

Familial aggregation:Familial aggregation:First degree relative 12%First degree relative 12%

HLA: DR2, DR3HLA: DR2, DR3 C1q, C2, C4C1q, C2, C4

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ENVIRONMENTALENVIRONMENTAL

Ultraviolet B lightUltraviolet B light

Sex hormones Sex hormones EstrogenEstrogen

Androgen Androgen Infectious agentInfectious agent

Drug Drug

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ApoptosisApoptosis

T-cellMacrophag

es

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ApoptosisApoptosis

DNA

Ro/ss-aSM

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ApoptosisApoptosis

T-cellMacrophag

es

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ApoptosisApoptosis

T-cellMacrophag

es

B cell

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PATHOGENESISPATHOGENESIS

UV Flare of SLE in 70% of patientsUV Flare of SLE in 70% of patients

Infections:Infections:Induce B and T cells Recognize self Ag Induce B and T cells Recognize self Ag Auto AbAuto Ab

EBV:EBV:

-- More common in SLE patients More common in SLE patients

-- Activate B cell Activate B cell

-- Amino acid sequences Mimic some Amino acid sequences Mimic some on DNA on DNA

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PATHOGENESISPATHOGENESIS

Female:Female: Ab responses than maleAb responses than male

OCP & HRT: Risk of SLE (1.2-2 fold)OCP & HRT: Risk of SLE (1.2-2 fold)

Estradiol T & B cell Activation & Estradiol T & B cell Activation & SurvivalSurvival

Prolonged immune Prolonged immune responseresponse

Bind to

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Genetic

Immune comlexes

Auto antigen

Apoptotic Material

Immunogenic Ag

Phagocytosis

Apoptosis

Environmental Factors

Auto antibody

B cellT cell

CD4DC

Complement activity

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CLINICAL CLINICAL MANIFESTATIONMANIFESTATION

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CLINICAL CLINICAL MANIFESTATIONMANIFESTATION

ANY ORGAN CAN BE AFFECTEDANY ORGAN CAN BE AFFECTED

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SYSTEMIC SYSTEMIC MANIFESTATIONMANIFESTATION

Fatigue, Malaise, Fever, Anorexia, Fatigue, Malaise, Fever, Anorexia, Weight lossWeight loss

95%95%

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MUSCULOSKELETALMUSCULOSKELETAL

Polyarthritis (95%)Polyarthritis (95%)Most patientsMost patientsHands, Wrists, Knees Hands, Wrists, Knees Deformity 10%Deformity 10%Erosion RareErosion Rare

Weakness (25%)Weakness (25%) MyositisMyositisGlucocorticoidGlucocorticoid Antimalaria Antimalaria

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SYSTEMIC SYSTEMIC MANIFESTATIONMANIFESTATION

Pain persist in a single jointPain persist in a single joint

Ischemic necrosis of boneIschemic necrosis of bone

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CUTANEOUSCUTANEOUS(80%)(80%)

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CUTANEOUSCUTANEOUS

Butterfly rash (50%):Butterfly rash (50%):

-- Most common Most common

-- Flare Flare

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CUTANEOUSCUTANEOUS

Discoid rash (DLE) (20%)Discoid rash (DLE) (20%)

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RENALRENAL

Nephritis (50%):Nephritis (50%):Most serious manifestationMost serious manifestation

U/A: any person with suspected SLEU/A: any person with suspected SLE

Class III or IV:Class III or IV:

-- Microscopic hematuria Microscopic hematuria

-- Proteinuria (> 500 Proteinuria (> 500 mg/24h) mg/24h)

-- HTN HTN

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HEMATOLOGICHEMATOLOGIC

Anemia (70%)Anemia (70%)Chronic diseaseChronic diseaseHemolytic Hemolytic

Leukopenia (65%)Leukopenia (65%)LymphopeniaLymphopeniaInfection: rareInfection: rareNot require therapyNot require therapy

Thrombocytopenia (15%)Thrombocytopenia (15%)

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PULMONARYPULMONARY

Pluritis (30%)Pluritis (30%)

-- Most common Most common

Interstitial inflammationInterstitial inflammation

Pulmonary hemorrhage Pulmonary hemorrhage

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CARDIACCARDIAC

Pericarditis (30%) Pericarditis (30%)

Myocarditis (10%)Myocarditis (10%)

Endocarditis (10%)Endocarditis (10%)Valvular insufficiencies Valvular insufficiencies

Libman-Sacks Libman-Sacks

Ischemia Ischemia

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VASCULARVASCULAR

Risk of vascular events 7-10 foldRisk of vascular events 7-10 fold TIA, Strok, MITIA, Strok, MI

Causes:Causes:APSAPSEmbolizationEmbolization

-- Carotid plaque Carotid plaque -- Libman-Sacks Libman-Sacks

VasculitisVasculitisAtherosclerosisAtherosclerosis

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GASTROINTESTINALGASTROINTESTINAL

PeritonitisPeritonitis

VasculitisVasculitis

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OCULAROCULAR

SiccaSicca

ConjunctivitisConjunctivitis

Retinal vasculitisRetinal vasculitis

Optic neuritis Optic neuritis

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NERVOUS SYSTEMNERVOUS SYSTEM

CentralCentral PeripheralPeripheral

Other causes Other causes

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ANTIPHOSPHOLIPID ANTIPHOSPHOLIPID SYNDROMSYNDROM

Risk ofRisk of

-- Clotting (arterial or venous) Clotting (arterial or venous)

-- Fetal loss Fetal loss Tests:Tests:

-- Anticardiolipin Anticardiolipin

-- Lupus anticoagulant Lupus anticoagulant

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ANTIPHOSPHOLIPID ANTIPHOSPHOLIPID SYNDROMSYNDROM

High titer of IgG ACLHigh titer of IgG ACL

- - Risk of clotting Risk of clotting

Diagnosis:Diagnosis:

-- One clinical One clinical

-- One test (repeated 12w One test (repeated 12w apart) apart)

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AUTOANTIBODIESAUTOANTIBODIES

Most patients 3 y or more before Most patients 3 y or more before symptomsymptom

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AUTOANTIBODIESAUTOANTIBODIES

FANA:FANA:Prevalence: 98%Prevalence: 98%

Best screaming testBest screaming test

Anti-dsDNA: Anti-dsDNA: Prevalence: 70%Prevalence: 70%

Specific (high titer) Specific (high titer)

Correlate with disease activityCorrelate with disease activity

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AUTOANTIBODIESAUTOANTIBODIES

Anti-Sm:Anti-Sm:

-- Prevalence: 25% Prevalence: 25%

-- Specific Specific

-- No clinical correlation No clinical correlation Anti-Ro (SS-A):Anti-Ro (SS-A):

-- Sicca, Neonatal lupus, Sicca, Neonatal lupus, NephritisNephritis

Antiphospholipid:Antiphospholipid:

-- 50% 50%

-- Criteria and APS syndrome Criteria and APS syndrome

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PATHOLOGYPATHOLOGY

Class I: Mesangial lupus nephritisClass I: Mesangial lupus nephritis

-- LM: NL LM: NL

-- IF: Mesangial deposit IF: Mesangial deposit

Class II: Mesangial prolipherativeClass II: Mesangial prolipherative

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PATHOLOGYPATHOLOGY

Class III: Focal proliferative Class III: Focal proliferative

Class IV: Diffuse proliferative Class IV: Diffuse proliferative

Class: V: MembranousClass: V: Membranous

Class: VI: Sclerotic Class: VI: Sclerotic

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DIAGNOSISDIAGNOSIS

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DIAGNOSISDIAGNOSIS

Malar rashMalar rash

Discoid rashDiscoid rash

Oral ulcerOral ulcer

PhotosensitivityPhotosensitivity

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DIAGNOSISDIAGNOSIS

Arthritis:Arthritis:NonerosiveNonerosive≥ ≥ 2 or more peripheral joints2 or more peripheral joints

Serositis:Serositis:Pleuritis or pericarditis Pleuritis or pericarditis

Renal:Renal:Proteinuria > 500 mg or ≥ 3+, or Proteinuria > 500 mg or ≥ 3+, or cellular castscellular casts

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DIAGNOSISDIAGNOSIS

Neurologic:Neurologic:Seizures or psychosis without other Seizures or psychosis without other causescauses

Hematologic:Hematologic:Hemolytic anemia orHemolytic anemia or

Leukopenia (< 4000) orLeukopenia (< 4000) or

Lymphopenia (< 1500) orLymphopenia (< 1500) or

Thrombocytopenia (< 100,000)Thrombocytopenia (< 100,000)

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DIAGNOSISDIAGNOSIS

Immunologic disorder:Immunologic disorder:Anti-dsDNA, anti-Sm, antiphospholipidAnti-dsDNA, anti-Sm, antiphospholipid

Antinuclear antibodies:Antinuclear antibodies:By immunofluorescence By immunofluorescence

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DIAGNOSISDIAGNOSIS

Criteria for classificationCriteria for classification

≥ ≥ 4 criteria4 criteria

Specificity: 95%Specificity: 95% Sensitivity: 75%Sensitivity: 75%

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DRUG-INDUCED LUPUSDRUG-INDUCED LUPUS

MilderMilder

Rarely renal or CNS involvementRarely renal or CNS involvement

Drugs: hydralazine, procainamidDrugs: hydralazine, procainamid……

Positive ANA and Anti histone but rarely Anti-Positive ANA and Anti histone but rarely Anti-dsDNAdsDNA

Reversible Reversible

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TREATMENTTREATMENT

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TREATMENTTREATMENT

No cureNo cure

Patients educationPatients education

Prophylactic measures:Prophylactic measures:Sunscreen Sunscreen

Low dose aspirin for antiphospholipid Low dose aspirin for antiphospholipid Ab positiveAb positive

Routine immunization Routine immunization

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TREATMENTTREATMENT

Glucocorticoids:Glucocorticoids:

-- For almost any manifestation For almost any manifestation

Immunomodulating agents:Immunomodulating agents:

-- Antimalaria Fever, Arthritis, Antimalaria Fever, Arthritis, CutaneousCutaneous

Prevents flarePrevents flare

-- Azathioprine Azathioprine

-- Mycophenolate mofetile Mycophenolate mofetile

-- Cyclophosphamide Cyclophosphamide

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CORSECORSE

Range from mild to sever diseases Range from mild to sever diseases Survival:Survival:

-- 95% at 5y and 78% at 20y 95% at 5y and 78% at 20y Causes of death:Causes of death:

-- First decade: disease activity, Renal, First decade: disease activity, Renal, InfectionInfection

-- After: Thromboembolic After: Thromboembolic Critical:Critical:

- - Nephritis, Cerebritis, Pulmonary Nephritis, Cerebritis, Pulmonary hemorrhage, hemorrhage,

Hematologic, CarditisHematologic, Carditis

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