244: Systemic Lupus Erythematosus Flashcards
What medication is given to all SLE patients as maintenance therapy (unless contraindicated) to reduce frequency and severity of flares?
Hydroxychoroquine
+/- DMARD depending on severity of disease
- Methotrexate
- Cyclophosphamide
- Azathiprine
- Belimumab
- Monoclonal antibody against B-cell activiating factor
- This is a new therapy
What is the most serious risk associated with neonatal lupus?
Which antibodies are most likely to cause neonatal lupus?
Neonatal heart block
Anti-SSA/Ro and Anti-SSB/La can cross the placenta
If they get trapped in the developing myocardium, they can cause complete heart block in-utero
What is the most important overall predictor of lupus mortality?
Renal damage
Which cytokines are major drivers of SLE?
- Innate immune system begins the cascade in response to apoptotic debris
- IFN-alpha
- B Cell Activating Factors
- TGF-beta
- IL-6
- Adaptive immune system sustains the inflammatory response
- IL-6
- TNF-alpha
What risk factors are associated with more severe SLE?
(When a person already SLE)
- Younger age of onset
- Male
- Racial/ethnic minority
- Lower socioeconimic status
What is the cardinal feature of lupus?
Production of ANA (antinuclear antibodies)
- Form circulating immune complexes that deposit in tissue
OR - Bind direcly to tissues in the body (ex: GBM)
What kind of lupus does this patient most likely have?
Acute cutaneous lupus erythematosus
- Classic malar rash: Butterfly rash on cheeks, extends onto nose
- Spares nasolabial folds; sharp demarcation
- Dermatomyositis does not spare nasolabial folds
- Variable appearance: erythema, edema, telangiectasia, erosions
- Triggered by sun exposure
- Associated with anti-dsDNA antibody, systemic disease
Which autoantibodies can cross the placenta and cause neonatal lupus in a growing fetus?
Anti-SSA/Ro
Anti-SSB/La
Which viral infections are associated with increased risk of lupus?
Epstein-Barr Virus (mono)
What are the key differences between natural autoantibodies and pathogenic autoantibodies?
- Natural
- Usually IgM
- Clear cellular debris effectively in healthy individuals
- Pathogenic
- Usually IgG
- Directly target cells through cross-reactivity with other antigens
What are the major causes of early vs. later causes of SLE mortality?
- Early mortality
- Severe SLE activity
- Infection
- Later mortality
- Cardiovascular diseaes
- Organ failure
- Infection
- Malignancy
What non-pharmacologic treatments are recommended for lupus?
- Sun avoidance
- Liver function surveilance
- Prophylactic abx and vaccinations
- Cardivascular screening
- Age-appropriate cancer screening
What form of lupus is this?
Discoid lupus erythematosus
Pink/brown scaly lesion
Annular w/central clearance
Heals with scarring and dyspigmentation
What laboratory findings would be consistent with a diagnosis of SLE?
- ANA
- Proteinuria
- Anemia (immune-mediated hemolytic)
- Leukopenia
- Thrombocytopenia
- Lymphopenia
- Other autoantibodies
- Anti-dsDNA
- Anti-Smith
- Anti-phospholipid
Describe the immune dysregulation that leads to SLE
- Impaired apoptosis and decerased clearance of apoptotic cells
-
Dendreditc cells present nuclear proteins
- Cytokines produced: (IFN-alpha, B-cell activiating factors)
- Activation and proliferation of autoreactive T and B cells
-
T cells
- Increased Th17 and Th2 cells = proinflammatory
- Decreased T-regs
-
B-cells
- Autoreactive, defective selection and signaling
- Differentiate to antibody-producing plasma cells
-
Immune complexes form between autoantibodies and self antigen
- Deposit in tissue, activate complement cascade
- -> Local inflammation and organ damage
