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
What are the therapeutic goals of lupus?
Induce remission
Maintenance therapy
Supportive therapy
What genetic factors contribute to SLE risk?
Cumulative effect of several genes
Some genes are asosciated with other autoimmune diseases in addition to lupus (STAT4, PTPN22)
A genetically susceptible person will develop SLE if exposed to certain/enough environmentla triggers
Which labs are predictive of SLE flare?
- Rising anti-dsDNA titers
- New evidence of complement consumption (low C3, C4)
- Increased ESR
- New lymphopenia
Which autoantibody is useful for tracking disease progression/clinical status of disease?
Anti-dsDNA
Which medication is the mainstay for acute SLE flares?
Corticosteroids
Good at stopping flares, but should not be used long-term
What is the role of ANA in the diagnosis of SLE?
Postive ANA is sensitve but not specific for SLE
- 95-99% of all patinets with SLE have a positive ANA
- People without SLE may also have a postive ANA
ANA is most useful in the diagnosis of lupus if pre-test probabilitiy is high