B4.071 Vasculitides Flashcards
what is vasculitis
inflammation and necrosis of blood vessels
etiology of vasculitis
infectious agents, mechanical, radiation, toxins HBV, HSV, CMV, parovirus serum sickness bacterial antigen autoantibodies: ANCA
pathogenesis of “noninfectious” vasculitis
- immune complex deposition in vessel wall
- antineutrophil cytoplasmic antibodies (ANCA)
- direct attack of endothelial cells by circulating anti-endothelial Abs
- cell mediated immunity (autoreactive T cells)
what are ANCAs antibodies against?
- neutrophil granules/monocyte lysosomes/endothelial cells
- anti-myeloperoxidase (MPO-ANCA) (p-ANCA)
- anti-proteinase-3 (PR3-ANCA) (c-ANCA)
- other
what diseases are MPO/p-ANCAs associated with
microscopic polyangiitis
Churg-Strauss Syndrome
what diseases are PR3/c-ANCAs associated with
granulomatosis with polyangiitis (GPA) (wegeners)
why are ANCAs measured?
track disease activity
what are some ways that vasculitis is classified
sixe of blood vessel location type nature of inflammatory infiltrate specific etiological factor immunopathogenic mechanism
large vessel vasculitides
Giant-cell arteritis
Takayasu arteritis
medium vessel vasculitides
polyarteritis nodosa
kawaski disease
small vessel vasculitides
granulomatosis with polyangiitis (GPA) (wegeners)
churg-strauss syndrome
microscopic polyangiitis
giant cell arteritis
focal, chronic, granulomatous inflammation of temporal artery
epidemiology of giant cell arteritis
old age (70-80 yr)
women > men
most common form of vasculitis
which arteries does giant cell arteritis primarily affect
temporal, cranial, aorta
pathogenesis of giant cell arteritis
T cell mediated
proinflammatory cytokines (TNFa)
HLA-DR4
pathology of giant cell arteritis
cordlike, nodular vessel w narrow lumen
granulomatous inflammation, plasma cells, multinucleated giant cells
necrosis, fragmentation of elastic lamina
fibrosis of media and thick intima
clinical features of giant cell arteritis
benign, self limiting
muscle aches
visual symptoms, diplopia, blindness
treatment of giant cell arteritis
steroids
anti-TNF
how does fragmentation of elastic lamina appear on histology?
blue stained lamina abruptly stops and occurs in segments rather than being continuous
takayasu arteritis
inflammatory disease of unknown etiology in large arteries (aorta and branches)
epidemiology of takayasu
young women
autoimmune?
pathology of takayasu
aorta and branches involved
thick intima, thick wall
panarteritis with giant cells
luminal narrowing, scarring
why is takayasu called pulseless disease
blood flow can’t reach extremities well
pulses cant be found
clinical features of takayasu
constitutional symptoms
high BP, asymmetry, weak pulse
ocular disturbances
treatment of takayasu
steroid
surgical reconstruction
polyarteritis nodosa (PAN)
acute necrotizing vasculitis of medium sized muscular arteries
epidemiology of polyarteritis nodosa
men > women
whites > blacks
etiology of polyarteritis nodosa
immune complex mediated damage of vessels
30% of PAN patients have chronic hep B
pathology of PAN
small to medium sized and large vessels
fibrinoid necrosis, mixed inflammatory cells
thrombosis, infarction of organ
clinical features of PAN
young adults
acute, subacute, or chronis
varies w affected site (kidney, heart, liver, GI)
constitutional symptoms, infarcts, necrosis
treatment of PAN
steroids
anti inflamm drugs
immunosuppressive agents
control hep B
unique characteristic of PAN
does NOT affect lungs
all other do
Kawasaki disease
acute necrotizing vasculitis of infancy and early childhood with fever, rash, conjunctival and oral lesions, and lymphadenitis
etiology of kawasaki
delayed hypersensitivity T cell reaction
infection with parovirus B19
Kawasaki epidemiology
85% in kids <5
95% in kids <10
clinical features of kawasaki
strawberry red tongue
red rashes on hands and feet
treatment of kawasaki
self limited
IVIg
aspirin
more serious complications of kawasaki
cardiac symptoms:
-coronary arteries affects, aneurysms, rupture, death
granulomatosis with polyangiitis (GPA) (wegeners)
systemic necrotizing granulomatous vasculitis of unknown etiology
organ systems affected by GPA
lungs
kidneys
upper resp tract
pathology of GPA
necrotizing vasculitis parenchymal/geographic necrosis granulomatous inflammation (T cell) small arteries, veins, capillaries crescentic glomerulonephritis (but could potentially not manifest in kidneys)
clinical features of GPA
males > females hematuria, proteinuria (renal disease) sinusitis (URT) pneumonitis, pulm infiltrate with cavitation (LRT) PR3-ANCA (over 90% of cases)
treatment of GPA
steroids
cyclophosphamide
anti-TNF
Churg-Strauss Syndrome
systemic vasculitis w prominent eosinophilia that occurs in young persons w asthma or allergy
pathology of churg strauss
necrotizing vasculitis of small and medium vessels
granulomas, eosinophilia, fibrinoid necrosis
similar to microscropic angiitis or PAN
MPO-ANCA (< half of cases)
organ systems affected by churg strauss
lungs kidney heart liver spleen CNS
differential for churg strauss
PAN parasitic, fungal infections GPA eosinophilic pneumonia syndrome drug vasculitis
treatment for churg strauss
steroids
anti-TNF
microscopic polyangiitis
a group of inflammatory vascular lesions affecting small vessels that are thought to represent a response to exogenous substances
localized and generalized forms
localized form of microscopic polyangiitis
skin
leukocytoclastic vasculitis
cutaneous vasculitis/venulitis
palpable purpura
what is the localized form associated with
drugs bacteria viruses TB bacterial endocarditis
pathology of localized form of microscopic polyangiitis
fibrinoid necrosis
acute inflammation (neutrophils)
extravasation of RBCs
generalized form of microscopic polyangiitis
systemic hypersensitivity polyarteritis
microscopic polyarteritis
what is the generalized form associated with
collagen vascular disease SLE RA HSP malignancy dysproteinemia
pathology of generalized form of microscopic polyangiitis
arterioles and small arteries
MPA-ANCA, PR3-ANCA
kidney, rapidly progressing glomerulonephritis and renal failure
skin involvement
microscopic features of leukocytoclastic vasculitis (localized microscopic polyangiitis)
fibrinoid necrosis of vessel wall intramural neutrophilic infiltrates leukocytoclasis (cell death) RBC extravasation involvement of small venules
thromboangiitis obliterans (bueger)
occlusive inflammatory disease of medium and small arteries in the distal arms and legs
epidemiology of buerger
smokers, young middle aged men
pathogenesis of buerger
smoking (tobacco products)
cell mediated immunity, collagen types 2, 3
genetic factors (Israeli, Indians, Japanese)
HLA A9, B5
pathology of buerger
acute inflamm of medium and small arteries
thrombosis, infarcts
segmental (acute or chronic)
gangrene, amputations
clinical features of buerger
25-40 y/o men, smokers
intermittent claudication, Raynaud phenomenon (loss of feeling and blueness of extremities)
painful ulcers, gangrene of toes/fingers
