2. Vasculitis
□ Vasculitis is a heterogeneous group of
disorders characterized by inflammation
and damage of the blood vessel.
□ Most vasculitides affect small vessels ranging in
size from arterioles to capillaries to venules.
□ The two common pathogenic mechanisms of
vasculitis are immune-mediated inflammation
and direct invasion of vascular walls by infectious
pathogens.
3. Vasculitis: Definition
▪ Inflammatorydestruction of blood vessels
▪ Infiltration of vessel wall with inflammatory cells
▪ Leukocytoclasis
▪ Elastic membrane disruption
▪ Fibrinoid necrosis of the vessel wall
▪ Ischemia, occlusion, thrombosis Aneurysm
formation
▪ Rupture, hemorrhage
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6. Pathogenesis
POTENTIAL MECHANISM
⦁ Immune complex formation and/or deposition
⦁ Anti Neutrophil Cytoplasmic Antibodies
production.(ANCA)
⦁ Antiendothelial cell Antibody mediated.
⦁ T lymphocyte activation with granuloma formation
7. Immune Complex-mediated
characterized by deposition of immune complexes in the vessel walls.
The antigen in the immune complex is not known in most of the cases.
Mechanism of tissue damage:
• The antigen-antibody (immune) complexes are formed when there is little
antigen excess.
• The immune complexes gets deposited in vessel walls → activate
complement system (e.g., C5a) → chemotactic for neutrophils →
phagocytose the immune complexes → release their contents → damage
the vessel wall.
• As the process becomes chronic, mononuclear cells infiltrate the vessel wall.
• The lumen of the involved vessel is narrowed → lead to ischemic changes
in the tissues supplied by the involved vessel
8. Immune Complex-mediated
Causes of immune-mediated vasculitis
• Systemic immunological diseases [e.g., systemic lupus
erythematosus (SLE) and polyarteritis nodosa].
• Drug hypersensitivity: Drugs themselves may be foreign proteins
(e.g.,streptokinase) or they bind to serum proteins (e.g., penicillin)
and behave like antigens.
• Secondary to viral infections: Viral proteins may form immune
complexes. Examples:
• Hepatitis B virus (HBV) associated polyarteritis nodosa (PAN).
• Cryoglobulinaemic vasculitis is strongly associated with hepatitis C virus (HCV)
infection
9. Antineutrophil Cytoplasmic Antibodies(ANCA)
Heterogeneous group of autoantibodies directed against certain proteins
(mainly enzymes) in the cytoplasmic granules of neutrophils and
monocytes.
Two important ANCAs are:
1. Anti-myeloperoxidase (MPO-ANCA): MPO is a lysosomal enzyme
normally involved in producing oxygen-free radicals. MPO-ANCAs can be
induced by drugs (e.g., propylthiouracil).
➢ Associated with microscopic polyangiitis and Churg–Strauss syndrome.
2. Anti-proteinase-3 (PR3-ANCA): PR3 is a constituent of neutrophil
azurophilic granule.
It shares homology with many microbial peptides and antibodies against
microbial peptides may form PR3-ANCAs.
➢ Associated with Wegener’s granulomatosis.
10. ⦁ Endothelial cells may express HLA II molecules at their
surface similar to antigen presenting cells.
(following activation by cytokines)
⦁ CD4+ T cells get activated following interaction
with these endothelial cells.
• Propogation of immunological processes resulting in
cell mediated injury, granuloma formation, delayed
hypersensitivity.
⦁ EXAMPLE:
⦁ Giant Cell (Temporal)Artritis
⦁ TakayashusArteritis
⦁ Wegners Granulamatosis
⦁ Churg- Strauss Syndrome
11. Antiendothelial Cell Antibodies
can produce endothelial cell injury and lysis through
either complement-mediated cytotoxicity or
antibody-dependent cellular cytotoxicity
. For examples, Kawasaki disease and systemic lupus erythematosus.
12.
13. Giant Cell (Temporal) Arteritis
□ chronic inflammatory disorder of large to
small-sized arteries
• principallyaffects arteries in the head—
especially the temporal arteries—butalso the
vertebraland ophthalmic arteries.
• Ophthalmic arterial involvement can lead
abruptly to permanent blindness;
• giant cell arteritisis a medicalemergency
requiring prompt recognition and treatment.
14. • T-cell–mediated immune response against
one of handful of vessel wall antigens that
drives subsequent proinflammatory cytokine
production (particularly TNF).
• Anti-endothelial cell and anti-smooth muscle
cell antibodies can also be demonstrated in
roughly two thirds of patients
• it is unclear whether these are causal or a
consequence of other immune injury.
15. □ A cellular immune etiology is supported by the
characteristic granulomatous response, a
correlation with certain MHC class II
haplotypes, and a prompt therapeutic
response to steroids.
16. MORPHOLOGY
□
Intimal thickening (with occasional thromboses) that
reduces the luminal diameter.
Classic lesions exhibit medial granulomatous
inflammation centered on the internal elastic lamina that
produce elastic lamina fragmentation;
There is an infiltrate of T cells (CD4+ CD8+) and
macrophages. Although multinucleated giant cells are
seen in approximately 75% of adequately biopsied
specimens
Granulomas and giant cells can be rare or absent.
□
□
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17. □ Inflammatory lesions are only focally distributed
along the vessel and long segments of relatively
normal artery may be interposed.
□ Healed stage marked by medial attenuation and
scarring with intimal thickening, typically with
residual elastic tissue fragmentation and adventitial
fibrosis.
18. Clinical Features.
□ Rare before age 50
□ Symptoms may be only vague and
constitutional—fever,fatigue, weight loss—or
there may be facial pain or headache, most
intense along the course of the superficial
temporal artery, which can be painful to
palpation.
□ Ocular symptoms (associated with
involvement of the ophthalmic artery) appear
abruptly in about 50% of patients;
22. Doctor, Doctor, my teenage son
coughed up blood
□ 15 y/o male with hx of chronic sinusitis and
congestion, here with complaints of hemoptysis
and dyspnea but stable now.
23.
24. Granulomatosis with Polyangiitis
□ Previously called Wegeners granulomatosis
Differential diagnosis
□
sarcoid
TB
Churg Strauss
□ Epidemiology of WGN
mostly kidney and lung with granuolomas
adults (4th and 5th decades) >>>kids
caucasians >>>noncaucasian
initially with respiratory symptoms and then renal insufficiency
25. Granulomatosis with Polyangiitis
□
□ Diagnosis: Clinical findings of sinusitis and pulm finding,
order high resolution CT. Check ANCA: (90% of WGN
have the marker) with 70% sensitivity
Bx:
lung: granulomas with geographic patterns of central
necrosis and accompanying vasculitis
renal: 10% with granulomas, segmental necrotizing GN
□ RX: rapid therapy needed
Steroids
cyclophosphamide
26. Showing features characteristic of granulomatosis with polyangiitis - a vasculitis and
granulomas with multi-nucleated giant cells.
27. Churg-Strauss Syndrome
□ Churg-Strauss syndrome is a small-vessel
necrotizing vasculitis classically associated with
asthma, allergic rhinitis,lung infiltrates, peripheral
hypereosinophilia, and extravascular necrotizing
granulomata.
□ Multisystem diseases with cutaneous involvement
(palpable purpura)gastrointestinal tract bleeding,
and renal disease (primarily as focal and
segmental glomerulosclerosis). Myocardial
involvement may give rise to cardiomyopathy
28. □ Lung and extrapulmonary
sites (skin, heart, nervous
system, GI) have prominent
eosinophilic infiltrate,
granulomatous reaction
around necrotic foci with
radially arranged histiocytes
and pallisadinggiant cells
near small arteries or
arterioles, eosinophilic
vasculitis
●May have fibrin-richedema,
lymphocytes, sarcoid-like
granulomas, focal fibrosis and
eosinophilic microabscesses
□
29. Behçet Disease
□ Behçet disease is a small- to medium-vessel
neutrophilic vasculitis that classically presents
as a clinical triad of recurrent oral aphthous
ulcers, genital ulcers, and uveitis.
30. Thromboangiitis obliterans
Buerger’s Disease
□
Thromboangiitis obliterans or Buerger's disease is a
segmental occlusive inflammatory condition of arteries
and veins, characterized by thrombosis and
recanalization of the affected vessels.
It is a non-atherosclerotic inflammatory disease affecting
small and medium sized arteries and veins of upper and
lower extremities.
The etiology of thromboangiitis obliterans is unknown,
but use or exposure to tobacco is central to the initiation
and progression of the disease.
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□
31. MORPHOLOGY
□ focal acute and chronic vasculitis of small-
and medium-sized arteries,predominantly of
the extremities.
□ Acute and chronic inflammation, accompanied
by luminal thrombosis.
• The thrombus can contain small
microabscesses composed of neutrophils
surrounded by granulomatous inflammation
32. Results of which of the following tests may
support the diagnosis of granulomatosis with
polyangiitis, eosinophilic granulomatosis with
polyangiitis, or microscopic polyangiitis?
A. Antineutrophil cytoplasmic antibody (ANCA) testing
B. Tests for serum C-reactive protein (CRP)
C. Erythrocyte sedimentationrate (ESR)
D. Measurement of serum albumin
33. Clinical Features
□ Early manifestations include cold induced Raynaud
phenomenon, leg pain induced by exercise that is
relieved on rest (intermittent claudication), instep foot
pain induced by exercise (instep claudication), and a
superficial nodular phlebitis.
Chronic extremity ulcerations develop, progressing over
time to frank gangrene. Smoking abstinence in the early
stages of the disease can often ameliorate further
attacks; however, once established, the vascular lesions
typically do not respond to smoking abstinence.
□
34. Infectious Vasculitis
□ Arteritis can be caused by the direct invasion
of infectious agents, usually bacteria
(Pseudomonas being the classic example) or
fungi, in particular Aspergillus and Mucor
species.
□ Vascular invasion can be part of a localized
tissue infection (e.g., bacterial pneumonia or
adjacent to abscesses).
35. □ Vascular infections can weaken arterial walls
and culminate in mycotic aneurysms, or can
induce thrombosis and infarction.
