Lupus Pathophysiology Flashcards
Define lupus erthemateux
illness in a patient with manifestations occuring in the skin
SLE is?
Major collagen vascular multisystem disease
SLE hallmark is?
development of autoantibodies to cellular nuclear components that leads to a chronic inflammatory autoimmune disease
SLE diagnosis requirements?
Test question
If 4 or more of the 11 criteria are documented, diagnosis can be made with 95% specificity and 85% sensitivty
SLE affects who?
Young adult woman
Genetic involvement in SLE
FOUR susceptibility genes are required for the expression of lupus
First degree relatives are about 20 times more likely
24&-58% concordance rate among identical twins
Targeted environmental agents that may induce SLE
Sunlight
Chemicals (hydrazine or aromatic amines)
Infxn (epstein barr virus)
Androgen and esterogen?
Androgen inhibits autoimmunity
Estrogen enhances autoimmunity
SLE Pathophysiology
Fluctuating multisystem disease with a clinical syndrome
Large spectrum of symptoms and organ involvement
Develop antibodies
Major event in the development of SLE?
Excessive autoantibody produces and the formation of immune complexes
What causes excessive autoantibodies?
Hyperactive B lymphocytes –> loss of immune self-tolerance and high atigenic load
Define antinuclear antibodies
Autoantibodies directed againsts nuclear constituents of the cell
Which antibodies are specific to SLE?
dsDNA antibodies
What are the four RNA associated antigens?
Smith
Small nuclear ribonucleoprotein
Ro
La
Two other against which antibodies can be formed?
Histone
Phospholipid moiety of prothrombin activator complex
Cardiolipin
Antiphospholipid antibodies
Lupus anticoagulant &
Anticardiolipin antibodies
What precedes the diagnosis of SLE by years?
Antinuclear
Anti-La
Anti-Ro
Antiphospholipid ab
What precedes SLE by months
Anti-Sm and anti-snRNP
Clinical Presentation of SLE
Major and minor joints with short durations (stiffneff, pain, inflammation)
Butterfly rash (sun exposure)
Filtrates
Pericarditis
Increase in coronary artery disease = increase in
SLE patients life expectancy
Lupus nephritis
A poorer outcome association and increased risk of morbidity/mortality
Six stages of the disease
Minimal Mesangial Mesangial Proliferative Focal Lupus Nephritis Diffuse Proliferative Lupus Nephritis Membranous Lupus Nephritis Advance sclerosing Lupus nephritis (global sclerosis)
SLE Diagnosis
Fluorescent antinuclear antibody test (ANA)
ANA test
Test question
Peripheral pattern of staining (rim) is characteristics of SLE
RIM is?
green around the periphery of the nucleus is characteristic of antibodies to double stranded RNA
SLE Treatment?
NSAIDS
Antimalarial drugs
Corticosteroids
Cytotoxic agents
Chloroquine and hydroxychloroquine
Manages cutaneous manifests, arthralgia, fatigue and fever
Best used in long-term management
Corticosteroids
Pulse therapy
For remission of SLE with life-threatening diseas
Cytotoxic agents
Cyclphosphamide and Azathiprine (steroid sparing)
Cyclophosphamide
Converted by P450 to active which forms irreversible DNA crosslinks between and within strands –> death
Cyclophosphamide Indication and ADME
Lupus nephritis and sever lupus
CYP450
Can lead to infxn or suppression of hematopoiesis
Azathioprine
Purine synthesis inhibitors
30-90% bioavailability
Can cause blood clots
Steroid sparing
