SYSTEMIC LUPUS SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)ERYTHEMATOSUS (SLE)

DEFINITIONDEFINITION

• Inflammatory diseaseInflammatory disease

• Multi-system diseaseMulti-system disease

• Autoimmune diseaseAutoimmune disease

CAUSE OF SLECAUSE OF SLE??? ??? • Environmental Environmental (infections, ultraviolet light, (infections, ultraviolet light,

extreme stress, certain drugs)extreme stress, certain drugs) • Genetic Genetic (SLE in families, histocompatibility (SLE in families, histocompatibility

antigens HLA-DR2 and HLA-DR3 )antigens HLA-DR2 and HLA-DR3 )

• Hormonal states Hormonal states (females, pregnancy, (females, pregnancy, delivery)delivery)

• Drugs Drugs (Chlorpromazine, Methyldopa, (Chlorpromazine, Methyldopa, Hydralazine, Procainamide, Isoniazid, Hydralazine, Procainamide, Isoniazid, Quinidine)Quinidine)

SLE - Pathogenesis

Susceptibility genes (usually multiple)

+

Triggering factors (probably environmental)

ABNORMAL IMMUNE RESPONSE

SLE - Pathogenesis

ABNORMAL IMMUNE RESPONSE

Hyperactive Hyperactive Inadequate T cells B cells regulatory

mechanism

Persistent pathogenic autoantibodies

Persistent pathogenic immune complexesPersistent damaging autoreactive T cells

SLE - Pathogenesis

• Pathogenic autoantibodies:

1. Directed to a host of self molecules in the nucleus and cytoplasm of cells, as well as on the cell surface.

2. Able to fix complement.

3. High avidity for the autoantigen present in target tissue.

EPIDEMIOLOGY OF SLEEPIDEMIOLOGY OF SLE• Frequency: 14.6/100,000 to 50.8/100,000Frequency: 14.6/100,000 to 50.8/100,000

• Incidence: 1.8-7.6/100,000 per year Incidence: 1.8-7.6/100,000 per year

• Internationally: worldwideInternationally: worldwide

• Age: 15-45 yearsAge: 15-45 years

• Gender: F/M = 9/1Gender: F/M = 9/1

• Race: blacks/ whites = 1/4Race: blacks/ whites = 1/4

TYPES OF LUPUSTYPES OF LUPUS

• Discoid LE/Subacute cutaneous LEDiscoid LE/Subacute cutaneous LE

• Systemic LESystemic LE

• Drug-induced LEDrug-induced LE

SYMPTOMS OF LUPUS (1)SYMPTOMS OF LUPUS (1)

• Fever (about 38° C), fatigue, weight loss - 90% Fever (about 38° C), fatigue, weight loss - 90% • Arthritis (swollen joints) - 90% Arthritis (swollen joints) - 90% • Skin rashes - 74% Skin rashes - 74% • Anemia - 71% Anemia - 71% • Kidney involvement - 50% Kidney involvement - 50% • Pain in the chest on deep breathing (pleurisy) - 45% Pain in the chest on deep breathing (pleurisy) - 45% • ““Butterfly” rash across the cheeks and nose - 42% Butterfly” rash across the cheeks and nose - 42%

SYMPTOMS OF LUPUS (2)SYMPTOMS OF LUPUS (2)

• Sun sensitivity (photosensitivity) - 30% Sun sensitivity (photosensitivity) - 30%

• Hair loss - 27% Hair loss - 27%

• Abnormal blood clotting problems - 20% Abnormal blood clotting problems - 20%

• Raynaud's phenomenon - 17% Raynaud's phenomenon - 17%

• Seizures - 15% Seizures - 15%

• Mouth or nose ulcers - 12%Mouth or nose ulcers - 12%

MALAR RASHMALAR RASH

DISCOID LUPUSDISCOID LUPUS

LUPUS RASHLUPUS RASH

LUPUS RASHLUPUS RASH

VASCULAR SKIN CHANGESVASCULAR SKIN CHANGES

RAYNAUD’S PHENOMENONRAYNAUD’S PHENOMENON LIVEDO RETICULARISLIVEDO RETICULARIS

SLE SKIN PATHOLOGYSLE SKIN PATHOLOGY

SEROSITIS IN SLESEROSITIS IN SLE

PLEURITISPLEURITIS PERICARDITISPERICARDITIS

ECHO IN PEICARDITISECHO IN PEICARDITIS

PERICARDIAL EFFUSIONPERICARDIAL EFFUSION

Lupus Nephritis

• Word Health Organization (WHO) Classification – based on histology and location of immune complexes.

1. Class I: Normal2. Class II: Mesangial3. Class III: Focal and segmental proliferative4. Class IV: Diffuse proliferative5. Class V : Membranous6. Class VI: Sclerosing

NEPHRITIS IN SLENEPHRITIS IN SLE

EM IN SLE NEPHRITISEM IN SLE NEPHRITIS

LUPUS DIAGNOSTIC CRITERIA (4/11)

• Malar rash Malar rash • Discoid rash Discoid rash • Photosensitivity Photosensitivity • Oral ulcers Oral ulcers • Arthritis (Arthritis (Nonerosive arthritis involving two or more peripheral joints) Nonerosive arthritis involving two or more peripheral joints)

• Serositis (Pleuritis or pericarditis )Serositis (Pleuritis or pericarditis )• Renal disorder (Renal disorder (Urine protein > 0.5 gm/day and/or cellular casts) Urine protein > 0.5 gm/day and/or cellular casts)

• Neurologic disorder (Seizures and/or psychosis)Neurologic disorder (Seizures and/or psychosis)• Hematologic disorder Hematologic disorder (Hemolytic anemia or leukopenia (<4000)or (Hemolytic anemia or leukopenia (<4000)or

lymphopenia (<1500) or thrombocytopenia (< 100,000) lymphopenia (<1500) or thrombocytopenia (< 100,000)

• Antinuclear antibody Antinuclear antibody • Immunologic disorder (Positive anti ds-DNA test, positive Immunologic disorder (Positive anti ds-DNA test, positive anti-Sm test, positive anticardiolipin or LAC)anti-Sm test, positive anticardiolipin or LAC)

LABORATORY TESTS IN LABORATORY TESTS IN SLESLE

• Antinuclear factorAntinuclear factor– Anti ds DNAAnti ds DNA– Anti SmAnti Sm– Anti Ro (SS-A)Anti Ro (SS-A)– Anti La (SS-B)Anti La (SS-B)

• False positive VDRLFalse positive VDRL• LAC (LAC (aPTT)aPTT) • Anticardiolipin (Anticardiolipin (ELISA test of anticardiolipin ELISA test of anticardiolipin

antibody for IgG, IgM, IgAantibody for IgG, IgM, IgA

ANTINUCLEAR ANIBODIESANTINUCLEAR ANIBODIES

HOMOGENOUS PATTERNHOMOGENOUS PATTERN SPECKLED PATTERNSPECKLED PATTERN

TREATMENTTREATMENT

• Non-steroidal Anti-inflammatory Drugs Non-steroidal Anti-inflammatory Drugs (NSAIDs) including COX 2(NSAIDs) including COX 2

• Corticosteroids (Prednisone, Solomedrol)Corticosteroids (Prednisone, Solomedrol)

• Antimalarials (Hydroxychloroquine)Antimalarials (Hydroxychloroquine)

• Immunomodulating Drugs (Imuran, Immunomodulating Drugs (Imuran, Endoxan, Methotrexate)Endoxan, Methotrexate)

• Anticoagulants (Aspirin, Coumadine)Anticoagulants (Aspirin, Coumadine)

PREGNANCY AND LUPUSPREGNANCY AND LUPUS

• Increased risk of disease activity during or Increased risk of disease activity during or immediately after (3 to 4 weeks) pregnancyimmediately after (3 to 4 weeks) pregnancy

• Antiphospholipid antibodies pose a particular Antiphospholipid antibodies pose a particular risk of miscarriagesrisk of miscarriages

• Congenital SLE (positive aRo/aLa mothers):Congenital SLE (positive aRo/aLa mothers):– Congenital heart blockCongenital heart block– Rash/photosensitivityRash/photosensitivity– ThrombocytopeniaThrombocytopenia

PROGNOSISPROGNOSIS• Mortality: Mortality:

– 10-year survival rates ranging from 75-85%10-year survival rates ranging from 75-85%– > 90% of patients surviving more than 5 years > 90% of patients surviving more than 5 years

• Early deaths: Early deaths: – InfectionInfection– Active diseaseActive disease– ThrombosisThrombosis– Renal failure Renal failure

• Late complications:Late complications:– AtherosclerosisAtherosclerosis– OsteoporosisOsteoporosis– Avascular bone necrosisAvascular bone necrosis– Dementia Dementia

Drug induced lupus

• More common in men than women.• Fatigue, fever, arthralgia and

pleuropericardial disease are common.• CNS and renal disease are very rare.• The clinical disease disappears after

withdrawal of the drug.• Anti-histone antibodies are found in 95% of

cases.

ANTI-PHOSPHOLIPID ANTI-PHOSPHOLIPID SYNDROMESYNDROME

• Thrombotic complications: deep venous Thrombotic complications: deep venous thrombosis, stroke, gangrene, heart attack, thrombosis, stroke, gangrene, heart attack, Libman-Sacks’Libman-Sacks’ endocarditisendocarditis

• MiscarriagesMiscarriages • Thrombocytopenia (low platelets count)Thrombocytopenia (low platelets count)• Blood clottingBlood clotting abnormalities ( abnormalities (lupus lupus

anticoagulant and anticardiolipin antibodyanticoagulant and anticardiolipin antibody))

8 to 65 percent of people with lupus have the lupus 8 to 65 percent of people with lupus have the lupus anticoagulant, and 25 to 61 percent have anticoagulant, and 25 to 61 percent have

anticardiolipin antibodyanticardiolipin antibody