1 IN THE NAME OF GOD

2 SYSTEMIC LUPUS ERYTHEMATOSIS (SLE)

3 DEFINITION Autoimmune Autoimmune Multisystem disease Multisystem disease Autoantibodies and immune complexes Autoantibodies and immune complexes

4 EPIDEMIOLOGY Women of child-bearing years (90%) Women of child-bearing years (90%) Most common age at onset: second and third decade Most common age at onset: second and third decade All ages and ethnic groups All ages and ethnic groups Both sexes Both sexes Prevalence in US /100,000 Prevalence in US /100,000 Prevalence in Iran 30/100,000 Prevalence in Iran 30/100,000

5 PATHOGENESIS

6 PATHOGENESIS Predisposition Susceptibility Genes Induction Autoimmunity Injury Clinical Disease Expansion

7 GENETIC BASIS Twins: Twins: Monozygotic 57% Dizygotic 5% Familial aggregation: Familial aggregation: First degree relative 12% HLA: DR2, DR3 HLA: DR2, DR3 C1q, C2, C4 C1q, C2, C4

8 ENVIRONMENTAL Ultraviolet B light Ultraviolet B light Sex hormones Sex hormonesEstrogenAndrogen Infectious agent Infectious agent Drug Drug

9 Apoptosis T-cell Macrophages

10 Apoptosis DNA Ro/ss-a SM

11 Apoptosis T-cell Macrophages

12 Apoptosis T-cell Macrophages B cell

13 PATHOGENESIS UV Flare of SLE in 70% of patients UV Flare of SLE in 70% of patients Infections: Infections: Induce B and T cells Recognize self Ag Auto Ab EBV: - More common in SLE patients - More common in SLE patients - Activate B cell - Activate B cell - Amino acid sequences Mimic some on DNA - Amino acid sequences Mimic some on DNA

14 PATHOGENESIS Female: Female: Ab responses than male Ab responses than male OCP & HRT: Risk of SLE (1.2-2 fold) Estradiol T & B cell Activation & Survival Prolonged immune response Prolonged immune response Bind to

15 Genetic Immune comlexes Auto antigen  Apoptotic Material Immunogenic Ag  Phagocytosis  Apoptosis Environmental Factors Auto antibody B cell T cell CD4 DC Complement activity

16 CLINICAL MANIFESTATION

17 CLINICAL MANIFESTATION ANY ORGAN CAN BE AFFECTED ANY ORGAN CAN BE AFFECTED

18 SYSTEMIC MANIFESTATION Fatigue, Malaise, Fever, Anorexia, Weight loss Fatigue, Malaise, Fever, Anorexia, Weight loss 95% 95%

19 MUSCULOSKELETAL Polyarthritis (95%) Polyarthritis (95%) Most patients Hands, Wrists, Knees Deformity 10% Erosion Rare Weakness (25%) Weakness (25%) Myositis MyositisGlucocorticoid Antimalaria Antimalaria

20 SYSTEMIC MANIFESTATION Pain persist in a single joint Pain persist in a single joint Ischemic necrosis of bone Ischemic necrosis of bone

21 CUTANEOUS (80%)

22 CUTANEOUS Butterfly rash (50%): Butterfly rash (50%): - Most common - Most common - Flare - Flare

23 CUTANEOUS Discoid rash (DLE) (20%) Discoid rash (DLE) (20%)

24 RENAL Nephritis (50%): Nephritis (50%): Most serious manifestation U/A: any person with suspected SLE Class III or IV: - Microscopic hematuria - Microscopic hematuria - Proteinuria (> 500 mg/24h) - Proteinuria (> 500 mg/24h) - HTN - HTN

25 HEMATOLOGIC Anemia (70%) Anemia (70%) Chronic disease Hemolytic Leukopenia (65%) Leukopenia (65%)Lymphopenia Infection: rare Not require therapy Thrombocytopenia (15%) Thrombocytopenia (15%)

26 PULMONARY Pluritis (30%) Pluritis (30%) - Most common - Most common Interstitial inflammation Interstitial inflammation Pulmonary hemorrhage Pulmonary hemorrhage

27 CARDIAC Pericarditis (30%) Pericarditis (30%) Myocarditis (10%) Myocarditis (10%) Endocarditis (10%) Endocarditis (10%) Valvular insufficiencies Libman-Sacks  Ischemia

28 VASCULAR Risk of vascular events 7-10 fold Risk of vascular events 7-10 fold TIA, Strok, MI TIA, Strok, MI Causes: Causes:APSEmbolization - Carotid plaque - Carotid plaque - Libman-Sacks - Libman-SacksVasculitisAtherosclerosis

29 GASTROINTESTINAL Peritonitis Peritonitis Vasculitis Vasculitis

30 OCULAR Sicca Sicca Conjunctivitis Conjunctivitis Retinal vasculitis Retinal vasculitis Optic neuritis Optic neuritis

31 NERVOUS SYSTEM Central Central Peripheral Peripheral Other causes Other causes

32 ANTIPHOSPHOLIPID SYNDROM Risk of Risk of - Clotting (arterial or venous) - Clotting (arterial or venous) - Fetal loss - Fetal loss Tests: Tests: - Anticardiolipin - Anticardiolipin - Lupus anticoagulant - Lupus anticoagulant

33 ANTIPHOSPHOLIPID SYNDROM High titer of IgG ACL High titer of IgG ACL - Risk of clotting - Risk of clotting Diagnosis: Diagnosis: - One clinical - One clinical - One test (repeated 12w apart) - One test (repeated 12w apart)

34 AUTOANTIBODIES Most patients 3 y or more before symptom Most patients 3 y or more before symptom

35 AUTOANTIBODIES FANA: FANA: Prevalence: 98% Best screaming test Anti-dsDNA: Anti-dsDNA: Prevalence: 70% Specific (high titer) Correlate with disease activity

36 AUTOANTIBODIES 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, Nephritis - Sicca, Neonatal lupus, Nephritis Antiphospholipid: Antiphospholipid: - 50% - 50% - Criteria and APS syndrome - Criteria and APS syndrome

37 PATHOLOGY Class I: Mesangial lupus nephritis Class I: Mesangial lupus nephritis - LM: NL - LM: NL - IF: Mesangial deposit - IF: Mesangial deposit Class II: Mesangial prolipherative Class II: Mesangial prolipherative

38 PATHOLOGY Class III: Focal proliferative Class III: Focal proliferative Class IV: Diffuse proliferative Class IV: Diffuse proliferative Class: V: Membranous Class: V: Membranous Class: VI: Sclerotic Class: VI: Sclerotic

39 DIAGNOSIS

40 DIAGNOSIS Malar rash Malar rash Discoid rash Discoid rash Oral ulcer Oral ulcer Photosensitivity Photosensitivity

41 DIAGNOSIS Arthritis: Arthritis:Nonerosive ≥ 2 or more peripheral joints Serositis: Serositis: Pleuritis or pericarditis Renal: Renal: Proteinuria > 500 mg or ≥ 3+, or cellular casts

42 DIAGNOSIS Neurologic: Neurologic: Seizures or psychosis without other causes Hematologic: Hematologic: Hemolytic anemia or Leukopenia (< 4000) or Lymphopenia (< 1500) or Thrombocytopenia (< 100,000)

43 DIAGNOSIS Immunologic disorder: Immunologic disorder: Anti-dsDNA, anti-Sm, antiphospholipid Antinuclear antibodies: Antinuclear antibodies: By immunofluorescence

44 DIAGNOSIS Criteria for classification Criteria for classification ≥ 4 criteria ≥ 4 criteria Specificity: 95% Specificity: 95% Sensitivity: 75% Sensitivity: 75%

45 DRUG-INDUCED LUPUS Milder Milder Rarely renal or CNS involvement Rarely renal or CNS involvement Drugs: hydralazine, procainamid … Drugs: hydralazine, procainamid … Positive ANA and Anti histone but rarely Anti-dsDNA Positive ANA and Anti histone but rarely Anti-dsDNA Reversible Reversible

46 TREATMENT

47 TREATMENT No cure No cure Patients education Patients education Prophylactic measures: Prophylactic measures:Sunscreen Low dose aspirin for antiphospholipid Ab positive Routine immunization

48 TREATMENT Glucocorticoids: Glucocorticoids: - For almost any manifestation - For almost any manifestation Immunomodulating agents: Immunomodulating agents: - Antimalaria Fever, Arthritis, Cutaneous - Antimalaria Fever, Arthritis, Cutaneous Prevents flare Prevents flare - Azathioprine - Azathioprine - Mycophenolate mofetile - Mycophenolate mofetile - Cyclophosphamide - Cyclophosphamide

49 CORSE 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, Infection - First decade: disease activity, Renal, Infection - After: Thromboembolic - After: Thromboembolic Critical: Critical: - Nephritis, Cerebritis, Pulmonary hemorrhage, - Nephritis, Cerebritis, Pulmonary hemorrhage, Hematologic, Carditis Hematologic, Carditis

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