VASCULITIS

DR MUDASSIRA
Associate Professor
Pathology Department
MIMC
LOs
 By the end of this session you will be able to:
 Classify vasculitis
 Describe the Pathogenic mechanisms of vasculitis
 Describe the morphological features of different
vasculitis
WHAT IS VASCULITIS ?

 An inflammation of the wall of a blood vessel

i.e vascular inflammatory injury
CONSEQUENCES OF VASCULITIS

 This inflammation may result in

 Narrowing of the vessel
 Occlusion of the vessel

 Weakening of the vessel wall which could lead to

an aneurysm and/or hemorrhage
TYPES OF VASCULITIS

Vasculitis can be classified by the

• Cause
• Location
• Type Of Vessel
• Size Of Vessel
• Histology
• Pathogenesis
• Clinical Manifestation
Presumptive etiology and typical sites
of common vasculitides
 vasculitis

small vessel
large vessel vasculitis
vasculitis medium vessel
vasculitis

delayed
hyper
sensitivity
reaction anti endothelial
cell antibodies
giant cell immune
complex kawasaki
arteritis disease
mediated
PAN
pauci imune
ANCA mediated immune
wegeners complex
granulomatosus mediated
Churg-Strauss SLE
syndrome
Pathogenesis

 Two most common pathogenic

mechanisms
 Non Infectious Vasculitis- Immune mediated
inflammation
 Infectious vasculitis: e.g syphilitic aortitis

 Others:
Physical and chemical injury e.g trauma, irradiation,
toxins
Non Infectious Vasculitis: Immune mediated
inflammation
Most systemic vasculitides probably have an
immune etiology:
1. Immune complex deposition

2. Antineutrophil cytoplasmic antibodies

3. Anti-endothelial cell antibodies

4. Autoreactive T cells
Immune complex deposition
 Immune reactants and complement can be
detected in the serum or vessels of patients
with vasculitis e.g.,
 DNA-anti-DNA complexes are present in the
vascular lesions of systemic lupus
erythematosus-associated vasculitis
 HBsAg- anti-HBsAg complexes in hepatitis-
induced vasculitis eg polyarteritis nodosa )
 Drugs act as haptens or antigens in
hypersensitivity reactions against drugs eg
penicillin, conjugate serum proteins streptokinase
Immune complex deposition
This muscular artery demonstrates vasculitis with
chronic inflammatory cell infiltrates.
The endothelial cells proliferation and
the lumen is absent
Systemic Lupus Erythematosis- SLE
Vasculitis

Leukoclastic

PAN
Antineutrophil cytoplasmic
antibodies

 Many small vessel vasculitides show a paucity

of vascular immune deposits and therefore
other mechanisms have been sought for these
so-called Pauci-immune vasculitides
Antineutrophil Cytoplasmic Antibodies

 ANCAs are a heterogeneous group of

autoantibodies directed against enzymes
mainly found within the

 primary granules in neutrophils

 in the lysosomes of monocytes

 in endothelial cells
Types of ANCA
Antineutrophil Cytoplasmic Antibodies

Classified as their target antigen

1. Anti-proteinase-3 (PR3-ANCA or cANCA):

 Found in primary granules in neutrophils

2.Anti myloperoxidase (MPO-ANCA or p-ANCA):

 Myeloperoxidase (MPO) is a lysosomal granule

constituent- involved in generating O2 free

radicals.
 Mechanism of Action of ANCA
Microbe antigens & Infections & drugs
drugs have induce antibodies
structure similar to which cross react
MPO or PR3 with MPO or PR3

Chemical mediators
These antibodies
from neutrophils
activate and
damage the
degranulate
endothelium and
neutrophils
vessel wall
Antineutrophil Cytoplasmic Antibodies

Importance:
 Useful quantitative diagnostic markers

 Degree of inflammatory activity

 Rise In Episodes Of Recurrence

Anti-endothelial Cell Antibodies

 Antibodies to ECs
 predispose to certain vasculitis e.g SLE and
Kawasaki disease
Anti-endothelial Cell Antibodies
Auto reactive T cells

T cells get activated and initiate type IV

hypersensitivity reaction and formation of
granulomas
Giant Cell (Temporal) arteritis
The most common form of vasculitis
 focal granulomatous inflammation of large
to small sized arteries
 chiefly cranial vessels

 most commonly the temporal arteries

 elderly people

 T cell mediated injury has been suggested

Temporal Arteritis
Gross morphology :

•Affects large to small

sized arteries, usually
branches of carotid artery
esp. temporal artery

•Temporal artery of a
patient with giant-cell
arteritis shows a
thickened, nodular, and
tender segment of a
vessel on the surface of
head (arrow)
 Temporal arteritis
Microscopy:
•Granulomatous
inflammation of media
with mononuclear
infiltrate and giant cells
•Internal elastic lamina
fragmentation,
A. Temporal art. Giant
cells in the media.
B. Elastic tissue stain
focal destruction of
internal elastic
membrane (arrow)
and intimal
thickening (IT)
Clinical manifestations:
 Unilateral throbbing headache
 Tender nodules along temporal artery course
 Jaw claudication- pain when chewing
 Impaired vision- cause occln of opth artery
 Poly Myalgia Rhumatica – pain & stiffness of
proximal muscles (Shoulder and pelvic muscles) most
commonly noted in mornings
 ?
Can anyone be alive without a

pulse
Takayasu Arteritis
 Granulomatous vasculitis of medium sized and
larger arteries characterized principally by
ocular disturbances and marked weakening of
the pulses in the upper extremities (pulseless
disease).
 Mostly affects young women, 30-50 yrs
 Takayasu arteritis
 Gross: Disease of medium &
large arteries
 Thickening of aortic arch or
proximal great vessels
 Pulmonary arteries
 coronary arteries
 A,
 Aortic arch angiogram narrowing
of brachiocephalic, carotid, and
subclavian arteries (arrows).
 B, cross-sections of
 the right carotid artery marked
intimal thickening with minimal
residual lumen.
Takayasu arteritis
 Microscopy: Mono nuclear infilt.
 Perivascular cuffing of vasa vasorum in adventitia
 medial necrosis and mononuclear inflammation in
wall
 granulomatous changes with giant cells
Clinical manifestations
 Fever
 Weak pulses in upper extremities pulseless disease
 Arthralgias, syncope, skin nodules, night sweats
claudications, bruits may be heard over the
subclavian arteries
 visual and neurologic disturbances
Polyarteritis Nodosa
 Segmental transmural Inflammation and
fibrinoid necrosis of small or medium-sized
muscular arteries
 Typically involves the renal and visceral
vessels and spares the pulmonary circulation.
 middle-aged men
PAN Morphology :
segmental fibrinoid necrosis and thrombotic occlusion of a
small artery. Note that part of the vessel (upper right, arrow) is
uninvolved
Polyarteritis Nodosa (cont,d)
The major features of this disease are
 Intestinal infarction and hemorrhage (bowel,
pancreas, gallbladder),
 Neuropathy

 Myalgia

 Severe renal involvement is found in 25 percent of

cases
Kawasaki disease Mucocutanious
L. node syndrome
 Mostly affects INFANTS & young CHILDREN , <5 yrs
 Morphology
 Gross: Affects small and medium sized arteries,
including coronary
 Microscopic: Transmural inflammation & necrosis of
vessel wall with inflammatory infiltrate
Clinical manifestations
 Fever, congested conjunctiva
 Muco-cutanious lesions- oral mucosa
 Cervical L adenopathy- usu one neck node
 Edema of hands and feet
 Erythema of palms and soles of feet
 Complications: myocarditis, coronary artery
aneurysm, which can rupture and lead to
death
Thromboangiitis Obliterans or
Buerger's Disease
 Inflammatory occlusive disease affecting
medium and small arteries and veins.
 Its prevalence is higher in Europe and Asia
 Males between 20 and 40 years old are most
commonly affected.
Thromboangiitis Obliterans or
Buerger's Disease
 Etiology: disease of smokers.
 Common complaints are claudication of the
foot or lower extremity, gangrene, or cyanosis
of the fingers and ulcers.
Raynaud phenomenon. A, Sharply demarcated pallor of the distal fingers
resulting from the closure of digital arteries. B, Cyanosis of the fingertips.
Thank
you