Lupus (exam 1) Flashcards
SLE
heterogenous illnesses that have in common the development of autoimmunity to self-nucleic acids and proteins
spectrum of SLE
skin-only disease to severe systemic involvement
SLE is characterized as a _______________ disease
chronic anti inflammatory
who is affected most by lupus?
women
starts at child bearing age
discoid lupus erythematous (DLE)
scarring that can be permanently disfiguring
limited to skin on head
subacute cutaneous and acute cutaneous lupus
highly photosensitive
nonscarring
acute cutaneous lupus erythematosus
malar rash
underlying visceral involvement
SLE nonspecific skin lesions
non scarring alopecia
mouth ulcers
photosensitivity
Raynaud’s phenomenon
deregulated IFN signaling
vasculitis/vasculopathy
neonatal lupus erythematosus
passive transfer of maternal IgG autoantibodies via placenta
diagnosed in pregnant females
what percentage of newborns with maternal autoantibodies develop NLE?
1%
clinical findings of NLE
cardiac
dermatologic
hematologic
hepatic
drug induced lupus associations
procainamide
hydralazine
Enbrel/remicade
minocycline
diltiazem
penicillamine
INH
quinidine
triggers of SLE?
excessive immune system activation
loss of tolerance of immune system
deregulated expression of components of immune system
deregulated estrogen metabolism
T cell lymphocytopenia
defect in switch from T helper 0 to T helper 2 cells
promotes B cell activation
environmental factors of lupus
UV light
viral infection (EBV, CMV)
hydralazine, INH, minocycline, anticonvulsants
immune dysregulation leading to SLE
hypergammaglobulinemia
complement deficiency
autoantibody production
cytokine activation
inability to clear immune complexes
organ/tissue deposition
malar
butterfly rash
symmetric
no scarring
SPARES nasolabial fold
1/2-1/3 onset
discoid
face, helix and scalp
asymmetric
demarcated papular lesions
scarring
alopecia
oral ulcerations are usually __________ and occur on the ___________
painless
hard palate or anywhere in buccal cavity
nose ulcerations occur on the _________ and can become a ___________
septum
asymmetric septal perforation
immunologic criteria for SLE
antinuclear antibody
anti ds DNA
anti smith antibodies
antiphospholipid antibody
low complement
direct Coombs test
individuals with identified genetic polymorphism are at ______________ for SLE compared to the general population
higher risk
what is a genetic signature of SLE?
up regulation of genes induced by interferons
In SLE, activation of complement and immune cells leads to
release of chemotaxins, cytokines, chemokine, vasoactive peptides and destructive enzymes
what contributes to irreversible tissue damage of glomeruli, arteries, lungs, in SLE?
accumulation of growth factors and products of chronic oxidation
key active treatment for SLE
hydroxychloroquine (Plaquenil)
active treatments for SLE
hydroxychloroquine
biologics (BenLysta)
cytotoxics
NSAIDs
Steroids
topical steroids
cytotoxics used to treat SLE
cellcept (mycophenolate)
cytoxan (cyclophos)
Imuran (azathioprine)
rituximab
NSAIDs used to treat SLE
advil
mobic
naproxen
steroids used to treat SLE
prednisone
medrol
preventative treatment for SLE
sunscreen (at least SPF 30)
nutritional supplements (calcium, vit D, folate)
Benlysta MOA
human monoclonal antibody
recognizes and blocks the biological activity of B-lymophocyte stimulator (BLyS)
BLyS
naturally occurring protein
B cell survival factor
elevated levels of BLyS _____________ of B cells which contribute to ______________
prolong the survival
production of autoantibodies
beneficial side effects of Benlysta
reduce circulating CD19, CD20, naive and activated B cells
memory cells increased initially and slowly declined
reduce IgG and anti-ds DNA
increase in complement C3 and C4
Hydroxychloroquine
anti malaria drug
antirheumatic
hydroxycloroquine is thought to act as a ___________________ (as an anti rheumatic) and it inhibits the production of ______________
mild immunosuppressant
rheumatoid factor and acute phase reactants
hydroxychloroquine accumulates in ___________ which stabilizes __________ and inhibits ______________
WBCs
lysosomal membranes
the activity of collegenases and proteases causing cartilage breakdown
maximum effectiveness of hydroxychloroquine is
3-6 months
half life of hydroxychloroquine
why is it this long?
537 hours (22.4 days)
extensive tissue uptake
metabolites of hydroxychloroquine
which is major?
desethylhydroxychloroquine (DHCQ) - major
desethylchloroquine (DCQ)
bidesethylhydroxychloroquine (BDCQ)
since hydroxychloroquine renal clearance does not correlate with creatinine clearance,
a dosage adjustment is not required for patients with renal impairment
hydroxychloroquine is higher in what type of cell?
mononuclear
what treatment for SLE is contraindicated in pregnancy?
cellcept (mycophenalate)
which drug has to be a lower dose if the person with SLE is thiopurine methyltransferase (TPMT) deficient?
azathioprine (Imuran)
which drug to treat SLE comes with a retinopathy risk?
Plaquenil
which drug to treat SLE can cause infertility in women and men?
cyclophosphamide (Cytoxan)
criteria for classification of SLE
SOAP BRAIN MD
serositis
oral ulcers
arthritis
photosensitivity
blood disorders
renal involvement
antinuclear antibodies
immunologic phenomena
neurologic disorder
malar rash
discoid rash
