Transcript Systemic_Lupus_Erythematosus

SYSTEMIC
LUPUS
ERYTHEMATOSUS (SLE)
DEFINITION
• Inflammatory disease
• Multi-system disease
• Autoimmune disease
CAUSE OF SLE ???
• Environmental (infections, ultraviolet light,
extreme stress, certain drugs)
• Genetic (SLE in families, histocompatibility
antigens HLA-DR2 and HLA-DR3 )
• Hormonal states (females, pregnancy,
delivery)
• Drugs (Chlorpromazine, Methyldopa,
Hydralazine, Procainamide, Isoniazid,
Quinidine)
SLE - Pathogenesis
Susceptibility genes (usually multiple)
+
Triggering factors (probably environmental)
ABNORMAL IMMUNE RESPONSE
SLE - Pathogenesis
ABNORMAL IMMUNE RESPONSE
Hyperactive
T cells
Hyperactive
B cells
Inadequate
regulatory
mechanism
Persistent pathogenic autoantibodies
Persistent pathogenic immune complexes
Persistent 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 SLE
• Frequency: 14.6/100,000 to 50.8/100,000
• Incidence: 1.8-7.6/100,000 per year
• Internationally: worldwide
• Age: 15-45 years
• Gender: F/M = 9/1
• Race: blacks/ whites = 1/4
TYPES OF LUPUS
• Discoid LE/Subacute cutaneous LE
• Systemic LE
• Drug-induced LE
SYMPTOMS OF LUPUS (1)
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Fever (about 38° C), fatigue, weight loss - 90%
Arthritis (swollen joints) - 90%
Skin rashes - 74%
Anemia - 71%
Kidney involvement - 50%
Pain in the chest on deep breathing (pleurisy) - 45%
“Butterfly” rash across the cheeks and nose - 42%
SYMPTOMS OF LUPUS (2)
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Sun sensitivity (photosensitivity) - 30%
Hair loss - 27%
Abnormal blood clotting problems - 20%
Raynaud's phenomenon - 17%
Seizures - 15%
Mouth or nose ulcers - 12%
MALAR RASH
DISCOID LUPUS
LUPUS RASH
LUPUS RASH
VASCULAR SKIN CHANGES
RAYNAUD’S PHENOMENON
LIVEDO RETICULARIS
SLE SKIN PATHOLOGY
SEROSITIS IN SLE
PLEURITIS
PERICARDITIS
ECHO IN PEICARDITIS
PERICARDIAL EFFUSION
Lupus Nephritis
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Word Health Organization (WHO) Classification
– based on histology and location of immune
complexes.
Class I: Normal
Class II: Mesangial
Class III: Focal and segmental proliferative
Class IV: Diffuse proliferative
Class V : Membranous
Class VI: Sclerosing
NEPHRITIS IN SLE
EM IN SLE NEPHRITIS
LUPUS DIAGNOSTIC CRITERIA (4/11)
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Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis (Nonerosive arthritis involving two or more peripheral joints)
Serositis (Pleuritis or pericarditis )
Renal disorder (Urine protein > 0.5 gm/day and/or cellular casts)
Neurologic disorder (Seizures and/or psychosis)
Hematologic disorder (Hemolytic anemia or leukopenia (<4000)or
lymphopenia (<1500) or thrombocytopenia (< 100,000)
• Antinuclear antibody
• Immunologic disorder (Positive anti ds-DNA test, positive
anti-Sm test, positive anticardiolipin or LAC)
LABORATORY TESTS IN
SLE
• Antinuclear factor
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Anti ds DNA
Anti Sm
Anti Ro (SS-A)
Anti La (SS-B)
• False positive VDRL
• LAC (aPTT)
• Anticardiolipin (ELISA test of anticardiolipin
antibody for IgG, IgM, IgA
ANTINUCLEAR ANIBODIES
HOMOGENOUS PATTERN
SPECKLED PATTERN
TREATMENT
• Non-steroidal Anti-inflammatory Drugs
(NSAIDs) including COX 2
• Corticosteroids (Prednisone, Solomedrol)
• Antimalarials (Hydroxychloroquine)
• Immunomodulating Drugs (Imuran,
Endoxan, Methotrexate)
• Anticoagulants (Aspirin, Coumadine)
PREGNANCY AND LUPUS
• Increased risk of disease activity during or
immediately after (3 to 4 weeks) pregnancy
• Antiphospholipid antibodies pose a particular
risk of miscarriages
• Congenital SLE (positive aRo/aLa mothers):
– Congenital heart block
– Rash/photosensitivity
– Thrombocytopenia
PROGNOSIS
• Mortality:
– 10-year survival rates ranging from 75-85%
– > 90% of patients surviving more than 5 years
• Early deaths:
– Infection
– Active disease
– Thrombosis
– Renal failure
• Late complications:
– Atherosclerosis
– Osteoporosis
– Avascular bone necrosis
– 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
SYNDROME
• Thrombotic complications: deep venous
thrombosis, stroke, gangrene, heart attack,
Libman-Sacks’ endocarditis
• Miscarriages
• Thrombocytopenia (low platelets count)
• Blood clotting abnormalities (lupus
anticoagulant and anticardiolipin antibody)
8 to 65 percent of people with lupus have the lupus
anticoagulant, and 25 to 61 percent have
anticardiolipin antibody