Lec 29 Pathology of Vasculitis Flashcards
What is vasculitis?
inflammation of blood vessel wall at least some point during course of disease
inflamed vessels –> vascular damage –> end organ damage
What are potential complications of vasculitis?
thickening, scarring, narrowing, weakening, thrombosis of affected vessel, aneurysm formation or rupture
How does vasculitis present?
constitutional symptoms [fever/myalgias/malaise] PLUS organ specific symptoms
What are 2 major categories of vasculitis by cause?
infectious = direct invasion and proliferation in vessel wall by pathogen
non-infectious = not known to be caused by direct vessel wall invasion by pathogen
What are some examples of infectious causes of vasculitis?
fungal
bacterial
rickettsial = rocky mountain spotted fever
What usually causes non-infectious causes of vasculitis?
most associated wtih immunological mech
What is treatment for infectious vs noninfectious cause of vasculitis?
non-infectious –> give immunosuppressive therapy b/c likely immune mediated
infectious = give antibiotic
What is large vessel vasculitis? 2 types?
vasculitis that affects aorta and major branches and analogous veins
- takayasu arteritis
- giant cell arteritis
What are the 7 categories of vasculitis?
- large vessel vasculitis
- medium vessel vasculitis
- small vessel vasculitis
- variable vessel vasculitis
- single organ vasculitis
- vasculitis associated with systemic disease
- vasculitis associated with probably etiology
What is medium vessel vasculitis? 2 types?
vasculitis that affects main visceral arteries, veins, and initial branches
- polyarteritis nodosa
- kawasaki disease
What is small vessel vasculitis?
vasculitis that affects intraparenchymal arteries, arterioles, capillaries, venules, veins
What are the 3 immune mech for non-infectious vasculitis?
- immune complex deposition
- anti-endothelial cell antibodies
- anti-neutrophil cytoplasmic antibody [ANCA]
What is mech of SLE causing vasculitis?
DNA-anti DNA complexes deposit in vessel walls
What is mech of polyarteritis nodosa [PAN] causing vasculitis?
in 30% of people have HBsAg-HBsAb complexes deposit
What are some drugs that cause immune complex deposition vasculitis?
streptokinase [directly]
penicillin [bound to proteins]
What is anti-neutrophil cytoplasm antibody [ANCA]?
ANCA is a circulating antibody that reacts with cytoplasmic antigens in neutrophils and endothelial cells
How are different types of ANCA classified?
by intracellular distribution –> either cytoplasmic [c-ANCA] or perinuclear [p-ANCA]
by target antigen –>
- MPO-ANCA is p-ANCA
- PR3-ANCA is c-ANCA
What is MPO? Where does MPO ANCA localize?
MPO = myeloperoxidase = a lysosomal granlue normally involved in generating oxygen free radicals
localizes to perinculear area = p-ANCA
What is PR3? Where does PR3 ANCA localize?
PR3 = proteinase 3 = a neutrophil azurophilic granule constituent
localizes to cytoplasm = c-ANCA
What is clinical use of measuring ANCA level?
good for diagnosis or management –> titers reflex disease activity so can monitor for recurrence
What is the major distinction between takayasu arteritis and giant cell arteritis?
takayasu = < 50 years
giant cell = > 50 years
How do you distinguish TAK and GCA histopathologically?
you can’t
Who usually gets temporal giant cell arteritis?
elderly > 50 yo female
What are signs of giant cell arteritis?
- may lead to irreversible blindness due to opthalmic artery occlusion
- most commonly affects branches of carotid artery
- high ESR
What are histo features of takayasu/giant cell arteritis
granulomatous thickening
- epithelioid macrophages
- giant cells = fusion of epithelioid macrophages
- collar of mononuclear cells [lymphocytes]
What artery should you biopsy to diagnose giant cell arteritis? What does negative biopsy tell you?
temporal artery biopsy
negative biopsy does not exclude a diagnosis b/c giant cell arteritis is extremely segmental
Who gets takayasu arteritis?
asian females < 40 yo
What are symptoms of takayasu arteritis?
“pulseless disease” = weak upper extremity pulses
fever, nigh sweats, arthritis, myalgias, skin nodules, ocular disturbances
latter sequelae of dialtion/narrowing/occlusion of aorta or branches
What are symptoms of giant cell arteritis?
have unilateral headache [from temporal artery], jaw claudication
What arteries commonly affected by takayasu arteritis?
aortic arch and proximal great vessels; commonly left subclavian
How do you diagnose takaysu arteritis?
- age of onset < 40 yo
- signs of limb ischemia
- decreased pulse in one or both brachial arteries
- difference in systolic BP between arms
- bruit in affected subclavian arteries
What treatment for giant cell arteritis?
corticosteroids with clinical suspicion even if not confirmed by biopsy
What treatment of takayasu arteritis?
corticosteroids in early stage of inflammation
vascular surgery in later stage for vascular dilation/narrowing etc
How does onset of MVV differ from that of LVV?
MVV is more acute and necrotizing
inflammatory aneurysms and stenoses are common
LVV = more gradual
Who gets polyarteritis nodosa?
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young adults
30% of pt are hep B positive
What are symptoms of polyarteritis nodosa?
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fever, weight loss, malaise, headache
varied symptoms; depend on which vessels involved
GI: ab main, melena
renal: HTN, renal damage
neuro dysfunction, cutaneous eruptions
What is polyarteritis nodosa?
necrotizing vasculitis
most frequently involves renal arteries –> arterial HTN and ischemic nephropathy
What vessels typically involved in polyarteritis nodosa?
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most frequently involves renal arteries –> ischemic nephropathy
may involve other organs but usually spares pulmonary circulation
Can you get glomerulonephritis from polyarteritis nodosa?
no! it does not involve glomerular capillaries
What patho features of polyarteritis nodosa?
- immune complex mediated
- 30% have chronic hep B –> immune complex deposition of HBsAg-HBsAb
- microaneurysms and spasm on arteriogram
What do you use to treat polyarteritis nodosa?
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corticosteroids
cyclophosphamide
What biopsy findings in polyarteritis nodosa?
- transmural inflammation of arterial wall with fibrinoid necrosis [bright pink]
- sparing of portions of vessel; see all stages of activity in same vessel at same time = ongoing and recurrent insults
- eventually get chronic inflammation and scarring
Who gets kawasaki disease?
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asian children < 4yo
infants and young children
What symptoms of kawasaki disease?
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acute fever, usually self-limited
+ mucocutaneous lymph node syndrome:
enlarged cervical lymph nodes, conjunctival injection, strawberry tongue, cracked lips, hand-foot erythema, desquamating rash
What disease is kawasaki associated with?
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mucocutaneous lymph node syndrome
What vessels primarily affected in kawasaki?
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coronary arteries –> coronary artery aneurysm, thrombosis –> MI, rupture
How do you treat kawasaki?
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IV immunoglobulin and aspirin
What is pathogenesis of kawasaki?
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due to autoantibodies to endothelial and smooth muscle cells
triggered by infection [usually viral] in genetically susceptible person
What is buerger disease?
segmental thrombosing vasculitis
in heavy smoker, male, < 40 yo
have intermittent claudication leading to gangrene, auto-amputation of digits, superficial nodular phlebitis
may have raynaud phenomenon
treat with smoking cessation
What are the 3 types of ANCA-associated vasculitis?
microscopic polyangitis = small vessel vasculitis
granulomatosis with polyangitis = small vessel vasculitis with granulomas
eosinophilic granulomatosis with polyangitis = small vessel vasculitis with granulomas and eosinophiles
What is triad of signs that characterizes granulomatosis with polyangitis [wegener’s]?
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- necrotizing granulomas in lung and upper airway
- focal necrotizing vasculitis most prominent in resp organs
- necrotizing glomerulonephritis = renal disease
What is mech of granulomatosis with polyangitis?
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possible T cell mediated hypersensitivity
PR3-ANCA/c-ANCA
What are symptoms of granulomatosis with polyangitis [wegeners]?
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upper respiratory tract: perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis
lower respiratory tract: hemoptysis, cough, dyspnea
renal: hematuria, red cell casts
What is outcome of granulomatosis with polyangitis [wegeners]? treat?
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die w/in 1 yr if untreated
treat: cyclophsophamide, corticosteroids
What is churg strauss syndrome?
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eosinophilic granulomatosis with polyangitis
- necrotizing vasculitis
- granulomas with eosinophils
- peripheral eosinophilia, asthma, allergic rhinitis
- assocaited wtih MPO-ANCA/p-ANCA
eosinophilic granulomatosis with polyangitis [EGPA] is associated wtih what type of ANCA?
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MPO-ANCA/p-ANCA
granulomatosis with polyangitis [GPA] is associated with what type of ANCA?
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PR3-ANCA/c-ANCA
What symptoms of churg-strauss syndrome?
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asthma, sinusitis, palpable purpura, peripheral neuropathy [wrist/foot drop]
can also involve heart, GI, kidneys [pauci-immune glomerulonephritis]
high IgE
Name the following
- Arteritis with Fever and mucocutaneous lymph node syndrome
- Usually
kawasaki disease = medium vessel vasculiits
Name the following:
- Necrotizing inflammation
Typically involving renal arteries but not glomerular capillaries, hence no glomerulonephritis
- Spares pulmonary vessels
- No ANCA
- 30% associated with chronic HBV infection
polyarteritis nodosa
medium vessel vasculitis
Name the following:
- Granulomatous inflammation; frequently involves the temporal artery, used for biopsy diagnosis
- Usually occurs in patients older than age 50
- Associated with polymyalgia rheumatica = prox muscle aches and weakness
giant cell arteritis
Name the following:
- Granulomatous inflammation, but diagnosis is clinical and radiologic
- Usually occurring in female patients younger than age 50
- “Pulseless disease” = b/c of initial manifestion
takayasu arteritis
Microscopic polyangitis symptoms?
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necrotizing vasculitis of lungs, kidneys, skin
pauci-immune glomerulonephritis and palpable purpura
similar to granulomatosis with polyangitis but without nasopharyngeal involvemtn
What type of ANCA associated wtih microscopic polyangitis?
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MPO-ANCA/p-ANCA
What is treatment fo microscopic polyangitis?
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cyclophsophamide and corticosteroids
What is henoch-schonlein purpura?
most common childhood systemic vasculitis
often follows URI
vasculitis seoncary to IgA complex deposition; associated wtih IgA nephropathy
What is triad of symptoms henoch-schonlein purpura?
skin = palpaple purpura on buttocks/legs
ahtralgias
GI: ab pain, melena, multiple lesions of same age
