Download Large Vessel Vasculitis: Mechanisms of Disease and Imaging

Large Vessel Vasculitis:
Mechanisms of Disease
and Imaging
Jaroslaw Nicholas Tkacz, M.D.
VASCULITIS
• ABERRANT IMMUNE RESPONSES THAT RESULT IN
INFLAMMATION AND NECROSIS OF BLOOD VESSELS –
ANEURYSM, STENOSIS, OCCLUSION AND
HEMORRHAGE
• TRIGGER – INFECTION, AUTOIMMUNE DISEASE,
UNKNOWN ANTIGEN
• CATEGORIZATION BY VESSEL TYPE – SMALL, MEDIUM,
LARGE
Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis
VASCULITIS – THE PLAYERS
Kawasaki
Behcets
Aortitis
Large
Rheumatoid arithritis
Takayasu
Giant-cell
Polyarteritis Nodosa
Med
Churg-Strauss
Wegeners
Cryoglobulinemic Vasculitis
Small
Henoch–Schönlein Purpura
Cutaneous Leukocytoclastic Ang
Anca-Associated SVV
VASCULITIS
GENERAL HALLMARKS
ELEVATED ACUTE-PHASE RESPONSES
SYSTEMIC INFLAMMATION
ESR
FEVER
CRP
MALAISE
WEIGHT LOSS
NIGHT SWEATS
MYALGIA
ARTHRALGIA
How does large vessel
vasculitis differ?
• Differs from others as it is mediated by CD4+ T cells,
antigen presenting cells and macrophages
• GCA and Takayasu have similar histologies but differ in
age of onset and vessels that are preferentially targeted
• No evidence of autoantibody component
• Transmural inflammation
– Vascular wall thickening
– Narrowing and obstruction of vessels
– Aneurysm formation, hemorrhage, dissection, rupture
Adventitia
CD4+ - Tcell
Activated dendritic cell
Giant Cell
INF-gamma
Macrophage
Media
Metalloproteinases
Reactive Oxygen intermediates
Perforin
Inflammation,
wall damage
Luminal
stenosis
PDGF
VEGF
Histology – Classic Vasculitis
I
M
Fibrinoid necrosis
Inflammation
Erythrocyte extravasation
A
GCA
Myofibroblast
proliferation,
endoluminal
stenosis
inflammation
I
PDGF
VEGF
Images courtesy of B. McCarthy, M.D., Lahey Clinic
M
A
Giant Cell Arteritis
• Systemic granulomatous arteritis
• Synonyms – temporal arteritis, cranial arteritis
• Differs from Takayasu
– Pt. age >50
– Increasing incidence with age peaking at 80
– Vascular distribution
• Preferential extracranial carotid distribution including internal
(opthalmic, posterior ciliary) and external (superficial temporal)
branches
• Tenderness or pulselessness of superficial temporal artery
• Elevated ESR
• Diagnosis usually established with typical clinical presentation and
temporal artery biopsy
American College of
Rheumatology Criteria for
Classification of Giant Cell Arteritis
(Note: visual changes not listed!)
Traditional (sensitivity, 93.5%; specificity, 91.2%; 3 0f 5 criteria must be met)
1.
Age of onset of 50 years or older
2.
Onset of new headache
3. Temporal artery tenderness or reduced pulsation
4.
Elevated (>50 mmHg) Westergren erythrocyte sedimentation rate
5.
Abnormal artery biopsy
Alternative (sensitivity, 95.3%; specificity, 90.7%; 3 of 6 criteria must be met)
1.
Age at onset of 50 years or older
2.
Onset of new headache
3. Temporal artery tenderness or reduced pulsation
4.
Claudication of jaw
5.
Scalp tenderness or nodules
6.
Abnormal artery biopsy
GCA –
Opthalmic Manifestations
Approximately 30%
•
•
•
Posterior ciliary arteritis can lead to anterior ischemic optic neuropathy (AION)
The most common cause of vision loss.
Ischemia of the optic nerve head (pallor of optic nerve)
– Supplied mainly by the posterior ciliary arteries
– TX- high dose corticosteroids
Chalky pallor of
ischemic optic
nerve
Fundoscopic exam
Image courtesy of B. McCarthy, M.D., Lahey Clinic
GCA- Imaging
Diagnosis based on biopsy
role of imaging in diagnosis not
established; imaging useful to
find other areas of vasculitis
Takayasu Arteritis
Adventitia
CD4+ - Tcell
Activated dendritic cell
Giant Cell
INF-gamma
Macrophage
Media
Metalloproteinases
Reactive Oxygen intermediates
Perforin
Inflammation,
wall damage
Luminal
stenosis
PDGF
VEGF
Slide image courtesy Paul Monach, MD, PhD, sec Rheumatology BUMC
Organized
endolumimal
thrombus
I
Too many blue
cells at the A/M
border Inflammation
M
A
Metalloproteinases
Reactive Oxygen intermediates
Perforin
Takayasu arteritis,
“Pulseless Disease”
• Involves large elastic arteries
– Thoracic aorta and major branches commonly
involved
• Adolescent girls and women 20-35 are at highest risk
• Most commonly seen in Japan, India, SE Asia and
Mexico
• N. A. 2.6 per million
• Most patients have diminished or no pulses in the
extremities because of subclavian stenosis/occlusion
aka “pulseless disease”
American College of Rheumatology Criteria
for the Classification of Takayasu Arteritis
•
Development of symptoms or findings related to Takayasu arteritis at age <40
years.
•
Claudication of extremities; worsening fatigue and discomfort in muscles of
one or more extremity while in use, especially the upper extremities
•
Decreased pulsation of one or both brachial arteries with BP difference of
>10mmHg in systolic blood pressure and between arms
•
Bruit over subclavian arteries or aorta; bruit audible on auscultation over one
or both subclavian arteries or abdominal aorta
•
IMAGING - Arteriographic narrowing or occlusion of entire aorta, its
primary branches or large arteries of the proximal or lower extremities, not
due to arteriosclerosis, fibro-muscular dysplasia or similar causes; changes
usually focal or segmental
•
Any three of the six criteria needed for the diagnosis
Imaging Takayasu Arteritis
• Anatomic Imaging
– CT, MRI, conventional Angiography
• Distribution, vessel stenosis, wall thickening (CT and MRI only)
and end organ damage
• Functional Imaging (active inflammation)
– MRI, FDG-PET
• Wall edema, delayed wall enhancement, high glucose metabolic
activity
Imaging Takayasu Arteritis
• We image all patients with MRI study
– Initial diagnosis, has replaced traditional angiography
– Follow-up studies for active inflammation, development of
stenosis and complications of large vessel vasculitis
• MRI Technique
– Axial T1 BB (for wall thickening)
– Axial STIR (for wall edema - active inflammation)
– Coronal T2 SS TSE (for mediastinum)
– Axial and coronal Balance FFE (for stenosis and low
eGFR)
– Coronal 3D T1 FFE pre and post gado with subtraction
imaging (for grading of stenosis, gauging active
inflammation and MIP image generation)
STENOSIS, >10 mmHg
SBP difference
MIP
Aortitis
Hypermetabolic
activity in
ascending aorta
Image courtesy Paul Monach, MD, PhD, sec Rheumatology, BUMC
Active Aortitis
Wall edema
STIR
STIR
Wall thickening
T1 BB
T1 BB
Aneurysm
PERFORIN
Wall edema,
aneurysm
STIR
Wall
thickening
T1 BB
Subclavian Steal
3D T1 FFE MIP
2D TOF
Stenosis, >25mmHg
SBP difference
Complications Despite Treatment Carotid Occlusion
Wall
thickening
T1BB
LCCA Occl
T1BB
TX Strategy –
Aortocarotid Bypass
Increasing CRP,
ESR – follow up
T1 BB
T1 BB
Active Inflammation,
Wall Edema
STIR
Early Phase Dynamic
Imaging
SUB 3D T1 FFE
Delayed Phase Wall Enhancement –
Active Inflammation
SUB 3D T1 FFE delayed phase
CT – Anatomic Imaging
Images courtesy Paul Monach, MD, PhD, sec Rheumatology BUMC
CT – Renal Artery, CA, SMA
Involvement
Images courtesy Paul Monach, MD, PhD, sec Rheumatology BUMC
Acute Chest Pain –
Pseudoaneurysm/
Dissection Formation
MIP
MPR
OTHER CONSEQUENCES
3D T1 FFE
T2 SS TSE
PA STENOSIS
3D T1 FFE
Conclusions
• Large vessel vasculitis is a CD4+ T-cell mediated immune response
to an unknown antigen
• Histologic pattern is similar for for both Takaysu and Giant-Cell
arteritis although anatomic distribution and demographics vary
• Takayasu affects large elastic arteries in the chest and abdomen
• Giant cell has a propensity for extracranial carotids (posterior ciliary
arteries, superfical temporal artery) although the aorta and other large
vessels can also be involved
• Pre-stenotic, early inflammation can be imaged with FDG-PET and
MRI
• Wall-thickening and vessel stenosis are later phases of disease and can
be imaged with CT, MRI or conventional angiography (stenosis only)
• Treatment - high dose immunomodulators with titration based on
disease activity per physical, lab marker and functional imaging
findings
References
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•
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Medium- and Large-Vessel Vasculitis, Mechanisms of Disease, Weyland and
Grozny, N Engl J Med 2003: 160-9.
Non-invasive imaging in the diagnosis and management of Takayasu’s arteritis, J
Andrews, A Al-Nahhas, D J Pennel, M S Hassain, K A Davies, D O Haskard, J C
Mason, Ann Rheum Dis 2004;63:995-1000.
Vascular Imaging with MRI: Inadequacy in Takayasu’s Arteritis Compared with
Angiography, AJR 146: 949-954, May 1986.
Giant-Cell Arteritis and Polymyalgia rhematica: usefulness of vascular magnetic
imaging studies in the diagnosis of aortitis, J Narvaez, J A Narvaez, J M Nolla, E
Sirvent, D Reina and J Valverde, Rheumatology 2005; 44:479-483.
Early diagnosis and follow-up of aortitis with [18F]FDG PET and MRI, J Meller, F
Strutz, U Dieker, A Scheel, C O Sahlmann, K Lehmann, M Conrad, R Vosshenrich,
European Journal of Nuclear Medicine and Molecular Imaging Vol. 30, No. 5, May
2003.
High-Resolution MRI of Giant-Cell Arteritis: Imaging of the Wall of the Superficial
Temporal Artery, T A Bley, O Wieben, M Uhl, J Thiel, D Schmidt, M Langer, AJR
2005; 184:283-287.