IN THE NAME OF GOD

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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 third Most common age at onset: second and third

decade 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 EstrogenEstrogenAndrogen 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 on Amino acid sequences Mimic some on

DNA 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 manifestationU/A: any person with suspected SLEU/A: any person with suspected SLEClass 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 cellular Proteinuria > 500 mg or ≥ 3+, or cellular castscasts

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DIAGNOSISDIAGNOSIS Neurologic:Neurologic:

Seizures or psychosis without other Seizures or psychosis without other causescauses

Hematologic:Hematologic:Hemolytic anemia orHemolytic anemia orLeukopenia (< 4000) orLeukopenia (< 4000) orLymphopenia (< 1500) orLymphopenia (< 1500) orThrombocytopenia (< 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 positiveRoutine 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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