1

IN THE NAME OF GOD

2

SYSTEMIC SYSTEMIC LUPUS LUPUS

ERYTHEMATOSIERYTHEMATOSISS

(SLE)(SLE)

3

DEFINITIONDEFINITION Autoimmune Autoimmune

Multisystem diseaseMultisystem disease

Autoantibodies and immune Autoantibodies and immune complexes complexes

4

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

5

PATHOGENESIPATHOGENESISS

6

PATHOGENESISPATHOGENESIS

PredispositionSusceptibility Genes

InductionAutoimmunity

InjuryClinical Disease

Expansion

7

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

8

ENVIRONMENTALENVIRONMENTAL Ultraviolet B lightUltraviolet B light

Sex hormones Sex hormones EstrogenEstrogenAndrogen Androgen

Infectious agentInfectious agent

Drug Drug

9

ApoptosisApoptosis

T-cellMacrophag

es

10

ApoptosisApoptosis

DNA

Ro/ss-aSM

11

ApoptosisApoptosis

T-cellMacrophag

es

12

ApoptosisApoptosis

T-cellMacrophag

es

B cell

13

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

14

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

15

Genetic

Immune comlexes

Auto antigen

Apoptotic Material

Immunogenic Ag

Phagocytosis

Apoptosis

Environmental Factors

Auto antibody

B cellT cell

CD4DC

Complement activity

16

CLINICAL CLINICAL MANIFESTATIONMANIFESTATION

17

CLINICAL CLINICAL MANIFESTATIONMANIFESTATION

ANY ORGAN CAN BE AFFECTEDANY ORGAN CAN BE AFFECTED

18

SYSTEMIC SYSTEMIC MANIFESTATIONMANIFESTATION

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

95%95%

19

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

20

SYSTEMIC SYSTEMIC MANIFESTATIONMANIFESTATION

Pain persist in a single jointPain persist in a single joint

Ischemic necrosis of boneIschemic necrosis of bone

21

CUTANEOUSCUTANEOUS(80%)(80%)

22

CUTANEOUSCUTANEOUS Butterfly rash (50%):Butterfly rash (50%): -- Most common Most common -- Flare Flare

23

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

24

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

25

HEMATOLOGICHEMATOLOGIC Anemia (70%)Anemia (70%)

Chronic diseaseChronic diseaseHemolytic Hemolytic

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

Thrombocytopenia (15%)Thrombocytopenia (15%)

26

PULMONARYPULMONARY Pluritis (30%)Pluritis (30%) -- Most common Most common

Interstitial inflammationInterstitial inflammation

Pulmonary hemorrhage Pulmonary hemorrhage

27

CARDIACCARDIAC Pericarditis (30%) Pericarditis (30%)

Myocarditis (10%)Myocarditis (10%)

Endocarditis (10%)Endocarditis (10%)Valvular insufficiencies Valvular insufficiencies Libman-Sacks Libman-Sacks

Ischemia Ischemia

28

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

29

GASTROINTESTINALGASTROINTESTINAL PeritonitisPeritonitis

VasculitisVasculitis

30

OCULAROCULAR SiccaSicca

ConjunctivitisConjunctivitis

Retinal vasculitisRetinal vasculitis

Optic neuritis Optic neuritis

31

NERVOUS SYSTEMNERVOUS SYSTEM CentralCentral PeripheralPeripheral

Other causes Other causes

32

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

33

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)

34

AUTOANTIBODIESAUTOANTIBODIES Most patients 3 y or more before Most patients 3 y or more before

symptomsymptom

35

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

36

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

37

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

38

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

39

DIAGNOSISDIAGNOSIS

40

DIAGNOSISDIAGNOSIS Malar rashMalar rash

Discoid rashDiscoid rash

Oral ulcerOral ulcer

PhotosensitivityPhotosensitivity

41

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

42

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)

43

DIAGNOSISDIAGNOSIS Immunologic disorder:Immunologic disorder:

Anti-dsDNA, anti-Sm, antiphospholipidAnti-dsDNA, anti-Sm, antiphospholipid

Antinuclear antibodies:Antinuclear antibodies:By immunofluorescence By immunofluorescence

44

DIAGNOSISDIAGNOSIS Criteria for classificationCriteria for classification

≥ ≥ 4 criteria4 criteria

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

45

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

46

TREATMENTTREATMENT

47

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

48

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

49

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

50