clinical manifestations of lupus
criteria for lupus
4 or more of these criteria
- malar rash
- discoid rash
- photosensitivity
- oral ulcers
- arthritis
- serositis
- renal disorder
- neuro disorder
- sero/immunological disorder
- pos ANA
what interaction is essential for lupus autoantibody formation?
CD40-CD40L - “second signal”
what do SLE autoantibodies do?
- cell destruction (bind to RBCs and Plts)
- cell “dysfuntion” (bind to vascular endothelium and neurons)
why are intermediate-size immune complexes so problematic?
large enough to activate complement
small enough to evade RES
lupus pts get them and can’t clear them
how do you detect immune complexes in skin biopsy of a lupus pt?
“the lupus band test”
anti-human antibody tagged w/ FITC (green flourescent dye - binds to pt’s antibody in dermal-epidermal junction
describe the rash in lupus
malar rash, discoid rash, photosensitivity
vascular problems in lupus
- raynaud’s w/ dilated nailfold capillaries
- vasculitis and ischemia/infarct: from IC deposition in arterial walls –> inflammation and damage –> ischemia and infarct
- digits, retina
describe typical lupus arthritis
PIP involvement w/ proliferative synovitis
lupus renal disease
extensive subendothelial deposits, scarred down glomerulus
full house staining
types: membranous lupus nephritis, mesangial proliferatie glomerulonephritis, membranoproliferative lupus nephritis, diffuse proliferative lupus nephritis
serositis in lupus
immune complex deposition –>
- pericarditis w/ pericardial effusion
- pleuritis w/ pleural effusion
- peritonitis with ascites (less common)
SLE neurologic manifestiaons
- psychosis
- seizures
- stroke
- cognitive function abnormalities
- transverse myelopathy
- mononeuritis multiplex
- organic brain syndrome
+ vasculopathy in the brain
what is antiphospholipid syndrome?
occurs in 25-50% of SLE pts (can also happen in non-lupus pts)
2 important tests: lupus anticoagulant & anticardiolipid antibody
sx: thromboiss, recurrent or late pregnancy loss, thrombocytopenia
tx: warfarin
what does antiphospholipid antibody do?
antibody (usually IgG) binds Beta-2-glycoprotein domain I, which is part of the natural immune system
sequence of events in lupus
- a break in tolerance to self-antigens
- production of autoantibodies to self
- formation of immune complexes
- difficulty clearing ICs
- tissue damage: 3 causes
- autoantibodies against target tissue
- autoantibodies directly causing “dysfunction”
- indirect innocent bystander organ damage
the most specific test for SLE
anti-ds-DNA
- 20-70% in pts w/ lupus
positive anti-ds-DNA is highly assoc w/ what complication?
glomerulonephritis!!
also some assoc w/ CNS disease
anti-smith antibody - what is it and utility?
- antibody to small nuclear ribosomal protein
- seen in 20-30% pts
- does not exist in other diseases - not sensitive, but very specific!!!
what is the tx of choice for lupus GN?
systemic steroids and cyclophosphamide
compare side effects of steroids and cytoxan
steroids: medium side effects, everyone gets them
cytoxan side effects: very bad, but not many people get them (cytopenias, malignancy)
rituxan for SLE
B cell depleting antibody
lots of clinical trials, all w/ bad results
some rheums use anyway
BLyS
- B cell survival factor
- produced by immune cells
- soluble form is active
- trimeric
late musculoskeletal complications of SLE
- Osteonecrosis
- Osteoporosis
important long term secondary problem in lupus
CAD: assoc w/ duration of disease
