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

Describe systemic lupus erythematosus

Systemic lupus erythematosus

  • Multi-system, inflammatory, autoimmune disease with diverse clinical and laboratory manifestations
  • Characterized production of autoantibodies which deposit in tissues and fix complement leading to inflammation and tissue damage
  • Variable course and prognosis - can be a mild, life-threatening, or anything in between

2

Lupus is most common in ____ and ____

Lupus is most common in women and African Americans

3

Risk factors for SLE are ____, ____, and ____

Risk factors for SLE are genetics, environmental, and female hormones/sex

 

  • Genetics: usually deficiency in several genes, usually SNPs in non-coding regions of DNA, only account for 15% of SLE heritability
  • Environmental: UV light, medications, viral infections (EBV), cigarette smoking
  • Female: increased disease activity in pregnancy

4

UV light promotes SLE through ____ and ____

UV light promotes SLE through DNA damage and keratinocyte apoptosis

5

Medications such as hydralazine and procainamide promote SLE through ____, leading to ____

Medications such as hydralazine and procainamide promote SLE through decrease DNA methylation, leading to altered gene expression

6

Describe SLE pathogenesis

SLE pathogenesis

  1. Genetic, environmental, immunoregulatory, hormonal, and epigenetic factors interact
  2. Immune complexes, antibodies, and cytokines released and T cells activated
  3. Various organs damaged

7

Describe immune dysregulation in SLE

SLE immune dysregulation

  • Impaired apoptosis with decreased clearance of apoptotic cells
  • Dendritic cells present self determinants -> stimulate activation and proliferation of autoreactive T cells and B cells, produce large amounts of interferon and B cell activating factors that sustain inflammatory response
  • T-cells: increased Th17 and Th2 cells (pro-inflammatory), decreased Tregs (anti-inflammatory)
  • Autoreactive B cells have defective selection and signaling: differentiate to plasma cells and produce autoantibodies
  • Immune complex formation between autoantibodies and self-antigen -> deposit in tissues -> activate complement cascade -> promote increased local inflammation and organ damage

8

Describe events of immune dysregulation in SLE

SLE immune dysregulation

  1. Genetic alterations and environmental exposures
  2. Impaired apoptosis
  3. Abnormally functioning dendritic cells, increased Th17 and Th2, decreased Treg, abnormally functioning B cells
  4. Production of autoantibodies, immune complex, and pro-inflammatory molecules
  5. Tissue injury

9

Describe disease-related immune events and associated polymorphisms in SLE

SLE disease-related immune events and associated polymorphisms

  1. Decreased clearance of apoptotic cell debris with nucleoprotein autoantigens
  2. Dendritic cell maturation, antigen presentation, cytokine proliferation
  3. T cell activation and B cell stimulation
  4. Plasma cell differentiation and autoantibody production

10

There is a _____ between the innate and adaptive immune systems

There is a feedforward loop between the innate and adaptive immune systems

11

All SLE patients have ____ 

All SLE patients have antinuclear antibodies (ANA)

 

 

(against various components of cell nucleus, detection by immunofluorescence, and reported as titer)

12

ANA is ____ but not ____ for SLE

ANA is sensitive but not specific for SLE

 

  • Patient with negative ANA is unlikely to have lupus even when presentation is suggestive because of high sensitivity
  • Most useful when pre-test probability for lupus is high because of low specificity

13

_____ and _____ are autoantibodies that are highly specific for SLE

Anti-dsDNA and anti-Sm are autoantibodies that are highly specific for SLE

14

SLE is characterized by _____ where autoantibody detection precedes diagnosis by many years

SLE is characterized by preclinical autoimmunity where autoantibody detection precedes diagnosis by many years

15

Pathogenic autoantiboidies are usually _____ and function to _____ and _____

Pathogenic autoantiboidies are usually IgG and function to form circulating immune complexes and directly target cells through cross-reactivity with other antigens

16

Anti-dsDNA causes kidney damage in renal lupus by _____, _____, and _____

Anti-dsDNA causes kidney damage in renal lupus by entrapping circulating immune complexes in the basement membrane, directly binding to basement membrane antigens, and directly binding to renal tubular cells

17

Anti-dsDNA _____ deposits are found in membranous disease while _____ deposits are found in proliferative disease

Anti-dsDNA subepithelial deposits are found in membranous disease while subendothelial deposits are found in proliferative disease

18

Anti-SSA and anti-SSB are associated with _____, _____, and _____

Anti-SSA and anti-SSB are associated with subacute cutaneous lupus, neonatal lupus, and complete heart block in utero

19

Describe signs and symptoms of SLE

SLE signs and symptoms

  • Malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, glomerulonephritis, neurologic disorder
  • Other rashes, non-scarring alopecia, lymphadenopathy, sicca (dry eyes and mouth), Raynaud's phenomenon, fever, transverse myelitis / mononeuritis multiplex, inflammatory myositis or myocarditis, interstitial lung disease
  • Pain, fatigue, memory thief / brain fog, depression

20

SLE is characterized by periods of _____ and _____

SLE is characterized by periods of flare (increased disease activity and inflammation) and remission (low level disease activity)

 

(variable flare rates for patients, labs are predictive of flare rates)

21

Describe SLE disease severity

SLE disease severity

  • Severe disease characterized by abrupt onset of symptoms, increased renal / neurologic / hematologic / and serosal involvement, and rapid accrual of organ damage (irreversible organ injury)
  • Factors associated with more severe disease: younger age of onset, male sex, race/ethnicity, lower socioeconomic status

22

SLE mortality is _____

SLE mortality is bimodal

 

  • Early causes: severe SLE disease activity, infections
  • Late causes: CVD, organ failure, infection, malignancy

23

Goals of therapy for SLE are ____, ____, and ____

Goals of therapy for SLE are induction of remission, maintenance therapy, and supportive therapy

 

  • Induction of remission: stop and reverse ongoing organ inflammation
  • Maintenance therapy: prevent or limit irreversible end-organ damage
  • Supportive therapy: prevent long-term complications from disease and treatment

24

Current therapy involves _____, _____, _____, and _____

Current therapy involves corticosteroids, hydoxychloroquine, immunosuppresants, and antiplatelet/anticoagulation (if antiphospholipid positive)

 

(also supportive therapy such as couseling on sun avoidance, liver function abd blood count surveillance, prophylactic antibiotics and vaccines, cardiovascular screening, age appropriate cancer screening, and osteoporosis screening and prevention)

25

Patients with SLE on treatment need to be monitored vigilantly because of the effects of _____

Patients with SLE on treatment need to be monitored vigilantly because of the effects of immunosuppressive medications

 

(liver dysfunction or drug-induced cytopenias, infection, cancer, infertility/birth defects)

26

_____ and _____ need to be monitored in SLE

Liver function and blood count need to be monitored in SLE

27

____ is a side effect of methotrexate

Transaminitis is a side effect of methotrexate

 

  • Monitor liver function

28

Positive ____ test is non-specific but common to patients with SLE

Positive ANA test is non-specific but common to patients with SLE

29

Cardinal pathogenic features of SLE is _____

Cardinal pathogenic features of SLE is development of autoantibodies that form circulating immune complexes and can also cause direct tissue inflammation

30

Combination of ____ and ____ is used to decrease disease activity and prevent organ damage in SLE

Combination of corticosteroids and DMARDs is used to decrease disease activity and prevent organ damage in SLE

 

(supportive therapies and monitoring strategies reduce preventable, long-term complications of disease)

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