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IBI Test 2 > B3.020 Big Case Systemic Lupus Erythematosus > Flashcards

B3.020 Big Case Systemic Lupus Erythematosus Flashcards

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1
Q

what is one of the most common presenting symptoms of lupus?

A

non destructive arthritis

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2
Q

what does it mean to be “non destructive”?

A

can straighten out joints that are deformed without pain

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3
Q

Jaccoud’s arthropathy

A

ligament laxity

can look like deformity is present, but can correct it on exam

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4
Q

describe serositis

A

pleural effusion
pericardial effusion
pleurisy/pleuritic chest pain

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5
Q

what is one way to check for serositis?

A

ultrasound of the heart to check for surrounding fluid

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6
Q

characterize oral ulcers associated with lupus

A

can be painless

can involve hard palate

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7
Q

what are three primary cutaneous clinical manifestations of lupus

A

Malar “butterfly” rash
subacute cutaneous lupus rash
discoid lupus rash

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8
Q

describe the butterfly rash

A

spares nasal labial fold

get the rash a few days after being in the sun

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9
Q

hematologic manifestations of lupus

A

anemia
thrombocytopenia
leukopenia
-can be secondary to lupus, related to comorbidities, or treatment for lupus

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10
Q

renal manifestations of lupus

A

glomerulonephritis (lupus nephritis)
multiple different mechanisms of actions
symptoms include: hematuria, proteinuria, hypertension, edema

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11
Q

describe the connection between lupus nephritis and type 3 hypersensitivity

A
  • consequence of soluble antigen-antibody complexes form in blood and deposit in the tissues
  • IgG containing immune complexes activate complement in tissues leading to damage (punches holes in basement membrane)
  • consumption of C3 and C4 which can be measured in blood
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12
Q

cardiac manifestation of lupus

A

pericarditis
Libman-Sack’s endocarditis
-noninfectious vegetations

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13
Q

what are noninfectious vegetations

A

can emobolize off an cause stroke, etc.

very different treatment options from infectious endocarditic, but cant always be differentiated

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14
Q

neurological manifestations of lupus

A

seizures

psychosis

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15
Q

what is synovitis

A

inflammation and swelling in joints

not specific to lupus

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16
Q

what is an antinuclear antibody

A

antibody with specificity to components of nucleus

indirect immunofluorescence is the preferred technique of detection

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17
Q

describe the process of ANA indirect immunofluorescence

A
  1. add patient plasma to microscope slide with attached cell
  2. wash to eliminate unattached antibodies
  3. add fluorescent tagged anti-human antibody
  4. assess if fluorescent signal present, continue until lowest dilution is still positive
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18
Q

how is the ANA indirect immunofluorescence test reported

A

reported as a titer which reflects dilution where result is still positive
start at 1:40 then 1:80 then 1:160

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19
Q

what are some limitations of ANA testing

A

positive in up to 15% of general population
variability in results between assays
quantitative value does not have clinical significance (does not trend with disease activity)

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20
Q

is ANA sensitive?

A

yes

few false negatives

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21
Q

is ANA specific?

A

no

high false positive

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22
Q

discuss anti-double stranded DNA antibodies

A

very specific for lupus
felt to be pathogenic
trend with disease activity in contrast to other antibodies

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23
Q

what are other specific antinuclear antibodies used in lupus diagnosis?

A

anti-smith
anti-RNP
anti-SSA (Ro)
anti-SSB (La)

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24
Q

what are antiphospholipid antibodies associated with?

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A

thrombosis

pregnancy loss

25
what are some functional assays of antiphospholipid antibodies?
Lupus anticoagulant Dilute Russell Viper Venom Test prolonged PTT
26
what are some other antiphospholipid antibodies that can be tested?
anti-cardiolipin IgM and IgG | anti-beta 2 glycoprotein 1 IgM and IgG
27
how is the complement system associated with lupus?
activation of the classical pathway is associated with flares of lupus disease activity leads to decline in C1-4
28
describe the classical complement pathway
initiated by Ag-Ab complexes (only IgG and IgM participate) C1q binds to Ch recruits C1r and C1s to form C1qr2s2 to cleave C2 and C4 to produce C4b2a (classic C3 convertase)
29
what types of medication can cause drug induced lupus?
hydralazine and procainamide (old cardiac drugs, not used much anymore) Isoniazid (TB) minocycline (used for acne treatment)
30
when do patients develop ANA and other autoantibodies relative to the diagnosis of lupus?
autoantibodies precede diagnosis by years
31
what is the acronym for ACR classification criteria
``` S-serositis O- oral ulcers A- arthritis P- photosensitivity M- malar rash D- discoid rash B- blood abnormalities R- renal abnormalities A- positive ANA I- immunologic abnormalities (dsDNA, Smith, cardiolipin) N- neurologic ```
32
what is drug induced lupus
associated with histone antibody most common manifestations are arthritis and pleurisy very unusual to have severe involvement such as renal or CNS involvement
33
can you have just cutaneous lupus?
yes | discoid or subacute cutaneous
34
discuss the epidemiology of lupus
``` 20-150 cases per 100,000 more common in women than men 15:1 women:men most commonly diagnosed between 16-55 ratio is lower in pediatric population and post-menopausal population ```
35
what races are more at risk for lupus?
Asians, African americans, African caribbeans, Hispanic americans
36
what are some suspected contributors to the pathogenesis of lupus?
``` genetics (gene mutations, epigenetics) hormones (female predominance) environmental factors (UV light) ```
37
what is the risk of lupus in identical twins?
14-57%
38
what are some categories of genetic polymorphisms that confer higher risk of lupus?
complement DNA degradation antigen presentation innate immunity/ interferon alpha
39
what are 3 contributors to the development of lupus
1. inefficient clearance of apoptotic debris 2. breach of tolerance 3. immune complex deposition and complement activation
40
why would inefficient clearance of apoptotic debris lead to lupus?
persistent cellular debris increases likelihood of the body creating antibodies against it
41
what are the 5 and 20 year survival rates of lupus?
>90% and 80% respectively
42
what is the leading cause of death in lupus patients?
cardiovascular disease (heart attacks)
43
what types of diseases are lupus patients at a higher risk of death from?
renal cardiovascular infection
44
why are lupus patients more at risk of infections?
immunosuppressant medications in addition to an already deficient immune system
45
what is the target of hydroxychloroquine therapy?
interfere with antigen processing and as a result peptide-MHC protein complexes
46
how does hydroxychloroquine interfere with antigen presentation?
multiple mechanisms interfering with lysosome acidification prevention of TLR binding epitopes
47
what is the target of Belimumab (Benlysta)?
autoantibody production/ B cell function
48
how does Belimumab interfere with B cell function?
blocks the binding of soluble B-cell activating factor (BAFF) also known as BLys (B lymphocyte stimulator)
49
what is the target of Azathioprine (Imuran)?
decrease function of B and T cells
50
how does Azathioprine decrease function of B and T cells?
pure analog which inhibits purine synthesis leading to inhibition of DNA and RNA results in reduced cellular proliferation, particularly leukocytes
51
how does Mycophenolate mofetil (CellCept) decrease function of B and T cells?
inhibits inosine monophosphate dehydrogenase which leads to reduced guanine monophosphate for purine synthesis in the de novo pathway used in proliferation of B and T cells
52
how does Cyclophosphamide (Cytoxan) decrease the function of B and T cells?
phosphoramide mustard attaches an alkyl group to DNA which ultimately leads to cell apoptosis traditional chemotherapy agent
53
discuss corticosteroid therapy for lupus
multiple mechanisms of action (genomic and nongenomic) | may inhibit interferon alpha
54
what are some consequences of corticosteroids?
``` weight gain decline in bone health DM infection risk mood (psychosis) ```
55
what meds are contraindicated in the situation of a potential pregnancy?
cyclophosphamide | mycophenolate mofetil
56
what tis the typical function of steroid treatment for lupus?
a bridge until the relief of the other drug is systemic | not a maintenance agent
57
what are some non-pharmacological treatments of lupus?
``` sun avoidance contraception high risk for CAD (exercise, low threshold to treat cholesterol) advise nicotine cessation immunizations screen for depression ```
58
what cues can help distinguish an infection from a lupus flare?
no worsening of other lupus symptoms complements improving compared to last visit CRP elevations (more typical of infection than lupus flare)
59
what prevents CRP elevation in a lupus flare?
IFNa

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