SM 232a - 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
Which populations are at greatest risk of SLE?
Women and racial/ethnic minorities
- Black women
- Hispanic women
- Native American women
- Asian women
- White women
How do we characterize SLE disease severity?
More severe disease will have…
- Abrupt onset of symptoms
- Increased renal, neurologic, hematologic, and serosal involvement
- Rapid accrual of organ damage
- Irreversible organ injury
- Ex: CKD or stroke
What are the three mechanisms for kidney damage in renal lupus?
Autoantibody = anti-dsDNA
- Circulating immune complexes become trapped in the GBM
- -> Glomerulonephritis
-
Pathogenic autoantibodies can bind directly to components of the GBM or antigens trapped in the GBM
- -> Glomerulonerphitis
-
Anti-dsDNA antibodies can bind directly to renal tubular cells
- -> Renal tubular injury
What environmental influences increase risk of SLE?
- UV damage
- DNA damage, keratinocyte apoptosis
- Medications via epigenetics
- Decreased DNA methylation
- Viral infections
- EBV
- Cigarette smoking
- Female hormones
- Increased disease activity durign pregnancy
What characterizes SLE disease activity?
- Progressively worsening disease
- Constant, stable disease state
- Periods of flare and remission
- Major flare at dianosis, usually followed by a lifetime of dormant disease
c. Periods of flare and remission
Which autoantibody is specific for lupus and associated with lupus nephritis?
Anti-dsDNA
What is systemic lupus erythematosus (SLE)?
Describe some of its characteristics
Multisystem, inflammatory, autoimmune disease
- Production of autoantibodies which deposit in tissues and fix complement
- -> Inflammation and tissue damage
- -> Range of clinical and laboratory manifestations
What exam findings would increase your suspicion for new-onset SLE?
Physical exam
- Malar rash
- “Butterfly rash” on cheeks
- Discoid rash
- Photosensitivity
- “Rash appeared while on vacation in Florida”
- Oral ulcers
- Inflammatory joint pain (arthritis)
- Changes to urine color, foamy urine
- Fever
- Fatigue
- Lymphadenopathy
Which autoantibodies have a high specificity for lupus?
Anti-dsDNA
Anti-Smith
