11/15 Diseases of Vasculature - Corbett Flashcards
vasculities
what is it
what might you see (3 things)
immune-mediated (inflammatory) desctruction of large, medium, and/or small blood vessels
- T cell response with granuloma formation
- immune complex deposition
- anti-neutrophil cytoplasmic antibodies (ANCAs - more a marker of disease than cause of it)
two main components of clinical presentation:
vasculitis
1. constitutional symptoms
- due to systemic inflammation
- fever, rash, myalgia, arthralgia, malaise, weight loss
2. vascular injury symptoms → depends on which vesc bed is involved!
- ischemia or infarction of affected organs
- thrombosis
- fibrosis
vasculitis by vessel size
large vessel vasculitis
- Takayasu arteritis
- Giant cell arteritis
medium vessel vasculitis
- Polyarteritis nodosa
- Kawasaki disease
immune complex small-vessel vasculitis
- cryoglobulinemic vasculitis
- IgA vasculitis (Henoch-Schönlein)
- hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)
ANCA-associated small-vessel vasculitis
- microscopic polyangiitis
- granulomatosis with polyangiitis (Wegener’s)
- eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
giant cell arteritis
aka temoral arteritis
- most common form of vasculitis in patients over 50
-
affects large and medium sized extracranial branches of carotid artery
- superficial temporal, vertebral, ophthalmic
pathogenesis
- all layers of artery affected
- CD4+ T cell mediated immune response
- characteristic granulomatous rxn, correlates with specific MHC class II haplotypes
- ends up destroying internal elastic lamina → ends up fragmented
giant cell arteritis
histo features
patho features
histological fts
- cell-mediated process
- dendritic cells
- T cells
- macrophages
- mononuclear cell infiltrates
- granuloma formation with multinucleated giant cells
pathological fts
- intimal thickening/fibrosis
- elastic lamina fragmentation
- granulomatous inflammation of media
- multinucleated giant cells (50-75% of specimens)
- SEGMENTAL (so you need to examine a large piece, at least 1cm)
giant cell arteritis
clinical presentation
age > 50
headache, jaw claidication, visual sx
constitutional sx (fever)
PE:
- scalp tenderness
- nodularity or tenderness or absent pulsations of temporal artery
- cardia exam and fundoscopic exam
lab:
- elevated Erythrocyte Sedimentation Rate
ESR
what is it?
what does incr ESR mean?
erythrocyte sedimentaion rate
rate at which RBCs suspended in plasma settle when placed in vertical tube (mm/hr) → incirect measure of Acute Phase Rxn (APR)
what does an increased ESR mean?
- systemic inflammation
- malignant neoplasms
- tissue injury/ischemia
- trauma
giant cell arteritis
major issue
effect tx
can cause OPTIC NERVE ISCHEMIA →→→ BLINDNESS
tx:
- start prednisone immediately (even without biospy result)
polymyalgia rheumatica
40-50% of patients with GCA have polymyalgia rheumatica
- affects elderly
- sx: proximal myalgia of hip and hsoulder girdles with accompanying morning stiffness lasting 1+ hr
- approx 15% with PMR → develop GCA
Takayasu’s arteritis
basics
pathophys
- primarily young women (25-35); 8:1 female to male affected
- most common Asia but occurs worldwide
-
granulomatous vasculitis of aorta, main branches, or pulmo artery
- most commonly affects aortic arch
- transmural fibrous thickening of aortic arch with severe luminal narrowing of major branch vessels
- “pulseless disease”need aortography for dx
- transmural fibrous thickening of aortic arch with severe luminal narrowing of major branch vessels
- most commonly affects aortic arch
pathophysiology
- irregular thickening of vessel wall with intimal hyperplasia → OCCLUSION
-
granulomatous inflammation with giant cells and patchy medial necrosis
- adventitial mononuclear infiltrates with perivascular cuffing of vasa vasorum
- intense mononuclear inflammation in media
- histology is indistinguishable from giant cell arteritis :/
Takayasu’s arteritis
clinical presentation
clinical presentation
- systemic sx occr early: fatigue, malaise, wt loss, night sweats, fever
- “pulseless disease” secondary to subclavian disease
- asymmetric bp, bruits, diminished pulses
- extremity claudication (pain with use of extremities)
- HTN, syncope, TIA stroke
comparison of giant cell arteritis and Takayasu’s
population affected (sex, age, ancestry)
primary vessels involved
acute vs chronic
what’s the same???
histopathology is same!
large vessel disease summary
2 types
- pathology
- vessels affected
- clinical features
polyarteritis nodosa
basics
pathophys
primarily affects adults in middle age (45-65)
necrotizing arteritis of medium (muscular) arteries
- arterioles, capillaries, and veins are NOT AFFECTED, which means…
- NO PULMO INVOLVEMENT
- NO GOLMERULONEPHRITIS (no RBC or casts)
pathophysiology
- lesions usually involve part of the vessel circumference with a predilection for branch points, leading to…
- disruption of internal and external elestic lamina (weakened arterial walls → potential for rupture/aneurysm)
- impaired perfusion with ulcerations, infarcts, ischemic atrophy, or hemorrhages
- lesions can be present at diff stages
- acute phase? transmural infl with fibrinoid necrosis → can lead to aneurysm
- if no healing, get massive fibrosis → nodule/node
polyarteritis nodosa
CP
tx
clinical presentation
- systemic inflammation
- fever, myalgias, weight loss
- mononeuritis multiplex (vasa nervorum) → neural deficits
- asymmetric, affecting both sensory and motor fx
- skin lesions (ex. palpable purpura) → signifies extravasation of RBCs outside blood vessels
- HTN (renal artery)
- abdominal pain and melana (ischemia)
very strong historical linkage to hepatitis B!!!
- positive HB surface antigen
treatment
- poor prognosis without tx
- 80% 5yr survival with tx
- mild? glucocorticoids
- moderate/severe? glucocorticoids + second immunosuppressive drug (ex cyclophosphamide)
Kawasaki disease
basics
pathophys
1 cause of acquired heart disease in children!
disease of medium size arteries
- 80% of patients < age 4
- predilection for coronary arteries
- unknown etiology
pathophysiology
- affects all arterial layers
- neutrophil influx, followed by IgA-secreting plasma cells
- intimal destruction can result in aneurysms → remodelling → thrombotic occlusion
Kawasaki disease
CP
clinical presentation
acute phase:
- unremitting fever (5+ days) in ALL PATIENTS
- high, spiking resistant to antipyretics: 7-14d duration
- conjunctival erythema
- maculopapular rash
- erythema and edema of palms and soles of feet with desquamation
- cervical lymphadenopathy
- changes in lips and oral cavity (dry/cracked lips, strawberry tongue)
treatment
- disease is typically self-limited, but in 25% of untreated → CAD
-
initial tx: IV immune globulin & aspirin
- decr infl
- more effective than ASA alone at preventing aneurysms
medium vessel disease
2 diseases
- pathology
- organs affected
- cilnical features
small vessel disease
granulomatosis with polyangiitis
mean age 40; M > F
PR3 (C)-ANCA positive
3 characteristic features
- necrotizing granulomas
- upper respiratory tract (ear, nose, sinuses, throat)
- 90% with nasal involvement : “saddle nose deformity”
- lower resp tract (lung)
- CXR: nodules/cavitation, “ground glass” appearance
- upper respiratory tract (ear, nose, sinuses, throat)
- necrotizing or granulomatous vasculitis
- affects caps, venules, arterioles, and arteries
- prominent in lungs and upper airways
- focal necrotizing glomerulonephritis
- rapidly progressive : asymptomatic hematuria
- few to no immune complexes
tx: glucocorticoids, and:
- methotrexate (mild disease)
- cyclophosphamide (mod-severe) or rituximab
small vasc disease 1
small vessel diseases 2
