1 IN THE NAME OF GOD
Dec 15, 2015
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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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