SM 232a - Systemic Lupus Erythematosus Flashcards Preview

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Flashcards in SM 232a - Systemic Lupus Erythematosus Deck (30)
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1
Q

What medication is given to all SLE patients as maintenance therapy (unless contraindicated) to reduce frequency and severity of flares?

A

Hydroxychoroquine

+/- DMARD depending on severity of disease

  • Methotrexate
  • Cyclophosphamide
  • Azathiprine
  • Belimumab
    • Monoclonal antibody against B-cell activiating factor
    • This is a new therapy
2
Q

What is the most serious risk associated with neonatal lupus?

Which antibodies are most likely to cause neonatal lupus?

A

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

3
Q

What is the most important overall predictor of lupus mortality?

A

Renal damage

4
Q

Which cytokines are major drivers of SLE?

A
  • 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
5
Q

What risk factors are associated with more severe SLE?

(When a person already SLE)

A
  • Younger age of onset
  • Male
  • Racial/ethnic minority
  • Lower socioeconimic status
6
Q

What is the cardinal feature of lupus?

A

Production of ANA (antinuclear antibodies)

  • Form circulating immune complexes that deposit in tissue
    OR
  • Bind direcly to tissues in the body (ex: GBM)
7
Q

What kind of lupus does this patient most likely have?

A

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
8
Q

Which autoantibodies can cross the placenta and cause neonatal lupus in a growing fetus?

A

Anti-SSA/Ro

Anti-SSB/La

9
Q

Which viral infections are associated with increased risk of lupus?

A

Epstein-Barr Virus (mono)

10
Q

What are the key differences between natural autoantibodies and pathogenic autoantibodies?

A
  • Natural
    • Usually IgM
    • Clear cellular debris effectively in healthy individuals
  • Pathogenic
    • Usually IgG
    • Directly target cells through cross-reactivity with other antigens
11
Q

What are the major causes of early vs. later causes of SLE mortality?

A
  • Early mortality
    • Severe SLE activity
    • Infection
  • Later mortality
    • Cardiovascular diseaes
    • Organ failure
    • Infection
    • Malignancy
12
Q

What non-pharmacologic treatments are recommended for lupus?

A
  • Sun avoidance
  • Liver function surveilance
  • Prophylactic abx and vaccinations
  • Cardivascular screening
  • Age-appropriate cancer screening
13
Q

What form of lupus is this?

A

Discoid lupus erythematosus

Pink/brown scaly lesion

Annular w/central clearance

Heals with scarring and dyspigmentation

14
Q

What laboratory findings would be consistent with a diagnosis of SLE?

A
  • ANA
  • Proteinuria
  • Anemia (immune-mediated hemolytic)
  • Leukopenia
  • Thrombocytopenia
  • Lymphopenia
  • Other autoantibodies
    • Anti-dsDNA
    • Anti-Smith
    • Anti-phospholipid
15
Q

Describe the immune dysregulation that leads to SLE

A
  • 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
16
Q

Which populations are at greatest risk of SLE?

A

Women and racial/ethnic minorities

  • Black women
  • Hispanic women
  • Native American women
  • Asian women
  • White women
17
Q

How do we characterize SLE disease severity?

More severe disease will have…

A
  • Abrupt onset of symptoms
  • Increased renal, neurologic, hematologic, and serosal involvement
  • Rapid accrual of organ damage
    • Irreversible organ injury
    • Ex: CKD or stroke
18
Q

What are the three mechanisms for kidney damage in renal lupus?

A

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
19
Q

What environmental influences increase risk of SLE?

A
  • UV damage
    • DNA damage, keratinocyte apoptosis
  • Medications via epigenetics
    • Decreased DNA methylation
  • Viral infections
    • EBV
  • Cigarette smoking
  • Female hormones
    • Increased disease activity durign pregnancy
20
Q

What characterizes SLE disease activity?

  1. Progressively worsening disease
  2. Constant, stable disease state
  3. Periods of flare and remission
  4. Major flare at dianosis, usually followed by a lifetime of dormant disease
A

c. Periods of flare and remission

21
Q

Which autoantibody is specific for lupus and associated with lupus nephritis?

A

Anti-dsDNA

22
Q

What is systemic lupus erythematosus (SLE)?

Describe some of its characteristics

A

Multisystem, inflammatory, autoimmune disease

  • Production of autoantibodies which deposit in tissues and fix complement
  • -> Inflammation and tissue damage
  • -> Range of clinical and laboratory manifestations
23
Q

What exam findings would increase your suspicion for new-onset SLE?

A

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
24
Q

Which autoantibodies have a high specificity for lupus?

A

Anti-dsDNA

Anti-Smith

25
Q

What are the therapeutic goals of lupus?

A

Induce remission

Maintenance therapy

Supportive therapy

26
Q

What genetic factors contribute to SLE risk?

A

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

27
Q

Which labs are predictive of SLE flare?

A
  • Rising anti-dsDNA titers
  • New evidence of complement consumption (low C3, C4)
  • Increased ESR
  • New lymphopenia
28
Q

Which autoantibody is useful for tracking disease progression/clinical status of disease?

A

Anti-dsDNA

29
Q

Which medication is the mainstay for acute SLE flares?

A

Corticosteroids

Good at stopping flares, but should not be used long-term

30
Q

What is the role of ANA in the diagnosis of SLE?

A

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

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