Transcript Slide 1 - Doctors2Be

Vasculitis
Dr. Gehan Mohamed
Dr. Abdelaty Shawky
* Definition:
• Inflammation of the blood vessels
• Clinically often include constitutional signs
and symptoms such as fever, myalgia,
arthralgia, and malaise, or local manifestations
of tissue ischemia.
* Causes of vasculitis:
1. infection: pathogens either cause direct
invasion of vascular walls or indirectly induce a
noninfectious, systemic immune-mediated
vasculitis, for example, by generating immune
complexes or triggering cross-reactivity.
2. Physical and chemical injury: such as
irradiation, mechanical trauma, and toxins can
also cause vascular damage.
3. immune-mediated vasculitis: the vascular wall
is damaged by different immune mechanisms;
a. Immune complex deposition: as in hypersensitivity
to drugs, hepatitis B virus infection
b. Anti-neutrophil cytoplasmic antibodies (ANCAs):
ANCAs are a heterogeneous group of autoantibodies
directed against enzymes mainly found within the
primary granules in neutrophils, in the lysosomes of
monocytes, and in endothelial cells.
- The description of these autoantibodies is based on the
immunofluorescent patterns of staining.
- Two main patterns are recognized: one shows
cytoplasmic localization of the staining (c-ANCA), and the
most common target antigen is proteinase-3 (PR3), a
neutrophil granule constituent. The second shows
perinuclear staining (p-ANCA) and is usually specific for
myeloperoxidase (MPO).
- The disorders characterized by circulating ANCAs are
called the ANCA-associated vasculitis.
c. Anti-endothelial cell antibodies:
• Antibodies to ECs, perhaps induced by defects in
immune regulation, may predispose to certain
vasculitis, such as those associated with SLE and
Kawasaki disease.
* Classification of vasculitis:
• The systemic vasculitis are classified on the
basis of :
- the size and anatomic site of the involved
blood vessels
- histologic characteristics of the lesion, and
- clinical manifestations.
There is considerable clinical and pathologic
overlap among these disorders
1. GIANT CELL (TEMPORAL) ARTERITIS
- Is the most common form of systemic vasculitis
in adults.
- Affects old ages above the age of 50 years.
- Is granulomatous inflammation of large sized
arteries.
- It affects principally the head arteries especially
the temporal arteries, but also the vertebral and
ophthalmic arteries and the aorta. Ophthalmic
arterial involvement may lead to permanent
blindness.
* Morphology:
• Characteristically, segments of affected arteries
develop nodular thickenings with reduction of
the lumen and may become thrombosed.
• Microscopically: granulomatous inflammation of
the inner half of the media showing mononuclear
infiltrate, multinucleate giant cells and
fragmentation of the internal elastic lamina.
• The healed stage reveals collagenous thickening
of the vessel wall with organization of the luminal
thrombus.
• Sometimes transforms the artery into a fibrous
cord.
* Pathogenesis: immunologic reaction against
elastin.
* Clinical Features:
- Constitutional manifestations: fever, fatigue,
weight loss.
- Facial pain or headache, often most intense
along the course of the superficial temporal
artery, which may be painful to palpation.
- Ocular symptoms (associated with involvement
of the ophthalmic artery).
2. TAKAYASU ARTERITIS
• The illness is seen predominantly in females
younger than age 40.
• This is a granulomatous vasculitis of large sized
arteries especially aorta and ocular arteries.
• Clinically characterized principally ocular
disturbances and marked weakening of the
pulses in the upper extremities (pulseless
disease).
* Morphology:
• Grossly: The affected vessel shows irregular
thickening with intimal wrinkling.
• Microscopically: adventitial mononuclear
infiltrate with perivascular cuffing of the vasa
vasorum and granulomatous inflammation, with
giant cells.
• Later, there is collagenous fibrosis involving all
layers of the vessel wall.
3. POLYARTERITIS NODOSA (PAN)
• PAN is a systemic vasculitis of small or mediumsized muscular arteries (but not arterioles,
capillaries, or venules), e.g. renal artery.
• Clinical manifestations result from ischemia
and infarction of affected tissues and organs.
• Affects young adults.
• The course may be acute, subacute, or chronic.
• The disease is fatal in most cases, either
during an acute fulminant attack or following
a protracted course, but therapy with
corticosteroids and cyclophosphamide results
in remissions or cures in 90% of cases.
* Morphology:
• Segmental transmural necrotizing
inflammation with neutrophils ,eosinophils
and fibrinoid necrosis.
• The lumen may become thrombosed.
• Later, the acute inflammatory infiltrate
disappears and is replaced by fibrous
thickening of the vessel wall that may extend
into the adventitia.
• Firm nodularity sometimes marks the lesions.
* Complications of PAN:
1. Thrombosis with subsequent ischaemic
complications.
2. Aneurysmal dilatation.
3. Rupture during acute attacks with fatal
hemorrhage.
4. KAWASAKI DISEASE (MUCOCUTANEOUS
LYMPH NODE SYNDROME)
- It is inflammation of the coronary arteries, usually in
young children and infants (80% of cases are <4 years
old).
- Epidemic in Japan.
- It is associated with the mucocutaneous lymph node
syndrome, an acute but usually self-limited illness
manifested by fever, conjunctival and oral erythema and
erosion, edema of the hands and feet, erythema of the
palms and soles, a skin rash often with desquamation,
and enlargement of cervical lymph nodes.
* Morphology:
• Fibrinoid necrosis and pronounced inflammation
affecting the entire thickness of the vessel wall.
* Fate:
• Most of cases subsides spontaneously or in
response to treatment.
• Some cases may be complicated by aneurysm
formation, thrombosis, and/or myocardial
infarction.
• Healed lesions may cause obstructive intimal
thickening
* Pathogenesis:
• Immune reaction characterized autoantibodies
to endothelial cells and smooth muscle cells,
leading to acute vasculitis.
• Viral infection may trigger the disease in
genetically susceptible patients.
5. MICROSCOPIC POLYANGIITIS
- It is necrotizing vasculitis affects arterioles,
capillaries.
- In contrast to PAN, the affected vessels are
smaller, necrotizing glomerulonephritis (90% of
patients) pulmonary capillaritis are particularly
common.
* Clinical features:
Hemoptysis, arthralgia, abdominal pain,
hematuria, proteinuria, hemorrhage, and muscle
pain or weakness.
* Pathogenesis:
- Immunologic reaction to an antigen such as
drugs (e.g., penicillin), microorganisms (e.g.,
streptococci), heterologous proteins, and tumor
antigens.
-In 70% of patients, p-ANCAs are present.
6.WEGENER GRANULOMATOSIS
It is a necrotizing granuloma affecting triad of:
1. Respiratory tract.
2. Necrotizing granulomatous vasculitis
affecting small to medium-sized vessels, mostly
of the lungs and upper airways.
(3) Kidney: in the form of glomerulonephritis.
8. THROMBOANGIITIS OBLITERANS
(BUERGER DISEASE)
• Is characterized by segmental inflammation and ,
thrombosis of medium-sized and small arteries,
principally the tibial and radial arteries
• Sometimes secondarily extending to veins and
nerves of the extremities.
• Affects heavy cigarette-smoking men and women
usually before age 35 in most cases.
• Direct endothelial cell toxicity by some
tobacco products or hypersensitivity to them.
• Stopping smoking in the early stages of the
disease often prevents further attacks.
8. VASCULITIS ASSOCIATED WITH
OTHER DISORDERS
• Such as rheumatoid arthritis, SLE, malignancy.
References:
Robbins and Cotran’s: Pathologic
Basis of Disease. Seventh edition.
Thanks