B3.020 Big Case Systemic Lupus Erythematosus Flashcards
what is one of the most common presenting symptoms of lupus?
non destructive arthritis
what does it mean to be “non destructive”?
can straighten out joints that are deformed without pain
Jaccoud’s arthropathy
ligament laxity
can look like deformity is present, but can correct it on exam
describe serositis
pleural effusion
pericardial effusion
pleurisy/pleuritic chest pain
what is one way to check for serositis?
ultrasound of the heart to check for surrounding fluid
characterize oral ulcers associated with lupus
can be painless
can involve hard palate
what are three primary cutaneous clinical manifestations of lupus
Malar “butterfly” rash
subacute cutaneous lupus rash
discoid lupus rash
describe the butterfly rash
spares nasal labial fold
get the rash a few days after being in the sun
hematologic manifestations of lupus
anemia
thrombocytopenia
leukopenia
-can be secondary to lupus, related to comorbidities, or treatment for lupus
renal manifestations of lupus
glomerulonephritis (lupus nephritis)
multiple different mechanisms of actions
symptoms include: hematuria, proteinuria, hypertension, edema
describe the connection between lupus nephritis and type 3 hypersensitivity
- 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
cardiac manifestation of lupus
pericarditis
Libman-Sack’s endocarditis
-noninfectious vegetations
what are noninfectious vegetations
can emobolize off an cause stroke, etc.
very different treatment options from infectious endocarditic, but cant always be differentiated
neurological manifestations of lupus
seizures
psychosis
what is synovitis
inflammation and swelling in joints
not specific to lupus
what is an antinuclear antibody
antibody with specificity to components of nucleus
indirect immunofluorescence is the preferred technique of detection
describe the process of ANA indirect immunofluorescence
- add patient plasma to microscope slide with attached cell
- wash to eliminate unattached antibodies
- add fluorescent tagged anti-human antibody
- assess if fluorescent signal present, continue until lowest dilution is still positive
how is the ANA indirect immunofluorescence test reported
reported as a titer which reflects dilution where result is still positive
start at 1:40 then 1:80 then 1:160
what are some limitations of ANA testing
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)
is ANA sensitive?
yes
few false negatives
is ANA specific?
no
high false positive
discuss anti-double stranded DNA antibodies
very specific for lupus
felt to be pathogenic
trend with disease activity in contrast to other antibodies
what are other specific antinuclear antibodies used in lupus diagnosis?
anti-smith
anti-RNP
anti-SSA (Ro)
anti-SSB (La)
what are antiphospholipid antibodies associated with?
thrombosis
pregnancy loss
what are some functional assays of antiphospholipid antibodies?
Lupus anticoagulant
Dilute Russell Viper Venom Test
prolonged PTT
what are some other antiphospholipid antibodies that can be tested?
anti-cardiolipin IgM and IgG
anti-beta 2 glycoprotein 1 IgM and IgG
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
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)
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)
when do patients develop ANA and other autoantibodies relative to the diagnosis of lupus?
autoantibodies precede diagnosis by years
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
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
can you have just cutaneous lupus?
yes
discoid or subacute cutaneous
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
what races are more at risk for lupus?
Asians, African americans, African caribbeans, Hispanic americans
what are some suspected contributors to the pathogenesis of lupus?
genetics (gene mutations, epigenetics) hormones (female predominance) environmental factors (UV light)
what is the risk of lupus in identical twins?
14-57%
what are some categories of genetic polymorphisms that confer higher risk of lupus?
complement
DNA degradation
antigen presentation
innate immunity/ interferon alpha
what are 3 contributors to the development of lupus
- inefficient clearance of apoptotic debris
- breach of tolerance
- immune complex deposition and complement activation
why would inefficient clearance of apoptotic debris lead to lupus?
persistent cellular debris increases likelihood of the body creating antibodies against it
what are the 5 and 20 year survival rates of lupus?
> 90% and 80% respectively
what is the leading cause of death in lupus patients?
cardiovascular disease (heart attacks)
what types of diseases are lupus patients at a higher risk of death from?
renal
cardiovascular
infection
why are lupus patients more at risk of infections?
immunosuppressant medications in addition to an already deficient immune system
what is the target of hydroxychloroquine therapy?
interfere with antigen processing and as a result peptide-MHC protein complexes
how does hydroxychloroquine interfere with antigen presentation?
multiple mechanisms
interfering with lysosome acidification
prevention of TLR binding epitopes
what is the target of Belimumab (Benlysta)?
autoantibody production/ B cell function
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)
what is the target of Azathioprine (Imuran)?
decrease function of B and T cells
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
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
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
discuss corticosteroid therapy for lupus
multiple mechanisms of action (genomic and nongenomic)
may inhibit interferon alpha
what are some consequences of corticosteroids?
weight gain decline in bone health DM infection risk mood (psychosis)
what meds are contraindicated in the situation of a potential pregnancy?
cyclophosphamide
mycophenolate mofetil
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
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
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)
what prevents CRP elevation in a lupus flare?
IFNa
