pathology of vascultiis

1. vasculitis

2. • Vasculitis: A general term for vessel wall inflammation.
• A group of disorders that damage or destroy blood vessels by
inflammation.
• The clinical findings are associated with the specific vascular bed
affected (site), and also there are signs and symptoms of general
inflammation, e.g. fever, myalgia, arthralgia and malaise.
• Grouping attempts have depended on vessel size, role of immune
complexes, presence of specific auto antibodies, granuloma
formation, tissue tropism, and other criteria.
• Considerable overlapping is present among these disorders.
Overview

5. Pathogenic mechanisms
1) Immune-mediated inflammation
(Noninfectious vasculitis).
2)Direct vascular invasion by infectious
pathogens (Infectious vasculitis)

6. Noninfectious
vasculitis
Immune complex
deposition
Antineutrophil
cytoplasmic
antibodies
Anti-endothelial cell
antibodies
AutoreactiveT cells

7. A) Immune complex-associated vasculitis: It is seen in
immunologic disorders, such as systemic lupus erythematosus
and includes:
1) Drug hypersensitivity vasculitis (e.g. penicillin and
streptokinase): Formation of antibodies against drug-modified
proteins (penicillin) or foreign molecules (streptokinase) results
in the formation of immune complexes.
2)Vasculitis secondary to infections : Formation of antibodies
against microbial constituents can result in formation of
immune complexes. (e.g. 30% of polyarteritis nodosa cases are
attributable to immune complexes composed of HBsAg
(Hepatitis B surface Antigen) and anti-HBsAg antibody.

8. B) Anti-neutrophil cytoplasmic antibodies (ANCAs) :They are
a heterogenous group of autoantibodies directed against constituents
of neutrophil primary grangules, monocytes lysosomes and endothelial
cells.They are important diagnostic tools.
The two most important ANCAs are:
1) Antiproteinase-3 (PR3-ANCA) , previously known as c-ANCA: Directed
against PR3, which is a constituent of neutrophil primary granules.The
PR3 shares homology with numerous microbial peptides!
e.g.Wegener Granulomatosis.
2) Anti- myeloperoxidase (MPO-ANCA) , previously known as p-ANCA:
Directed against MPO, which is a lysosomal granule constituent
involved in FOR formation and proteolytic enzymes. MPO-ANCAs are
induced by several therapeutic agents, especially (Propylthiouracil).
e.g. Microscopic polyangiitis,Churg-strauss syndrome.

9. • The vascular lesions do not typically contain antibodies or complements,
therefore ANCA vasculitides are sometimes called “pauci- immune”
C) Anti-endothelial cell antibodies: such as Kawasaki Disease.
D) AutoreactiveT-cells : Giant cell arteritis.

10. Giant Cell (Temporal)
Arteritis

11. Overview
• Most common form of vasculitis among the elderly in developing
countries.
• Chronic, typically granulomatous inflammation.
• Large to small size arteries, mainly those supplying the head-
particularly the temporal arteries.
• Vertebral and ophthalmic arteries and the aorta (giant cell aortitis)
also can be involved.

13. Pathogenesis
• T cell-mediated immune response to an as-yet
uncharacterized vessel wall antigen.
• Pro-inflammatory cytokines (especiallyTNF) and anti-
endothelial cell antibodies also contribute.

14. Morphology

16. Clinical Features
- Rarely seen before the age of 50.
- General inflammation symptoms (fever, fatigue, weight loss, etc..)
- Facial pain or headache along the superficial temporal artery, which is painful to
palpation.
- Ocular symptoms (in 50% of patients), ranging from diplopia to complete vision
loss.
- Corticosteroids and anti-TNF therapies are effective.

18. TakayasuArteritis
(Pulseless Disease)

19. Overview
- Granulomatous vasculitis of medium sized and larger arteries.
- Characterized by ocular disturbances and marked weakening of the pulse in the
upper extremity (hence the alternate name).
- Transmural scarring and thickening of the aorta – particularly the arch and great
vessels, with severe luminal narrowing of the major branch vessels.
- With the shared characteristics among it andTemporalArteritis, distinction is
done by considering the age (younger than 50).
- Autoimmune etiology.

22. Morphology

23. Clinical features
- Non-specific symptoms initially.
- Vascular symptoms predominate later on, including reduced
blood flow to the extremities, ocular disturbances, leg
claudication, and pulmonary hypertension.
- Narrowing of the coronary arteries can lead to MI, and
systemic hypertension is present in roughly 50% of patients
with renal artery involvement.

24. Polyarteritis Nodosa (PAN)

25. Overview
- It’s a systemic vasculitis of small or medium – sized blood vessels.
- It typically involves renal and visceral vessels.
- It spares the pulmonary circulation.
- NoANCAs’ association , but 1/3 of the cases have chronic hepatits B
infection, leading to the formation of immune complexes containing
hepatitis B antigen in infected vessels.

27. Morphology

28. Clinical features
- The clinical course may range from acute to chronic but typically is
episodic with long symptoms-free intervals.
- Systemic findings are nonspecific.
- A “classic” Presentation includes a combination of hypertension,
abdominal pain and bloody stools, diffuse muscular aches and peripheral
neuritis, predominantly affecting motor nerves.
- Immunosuppression can yield remission or cure in 90% of the cases.

29. Kawasaki Disease

30. Overview
- Acute, febrile, usually self-limiting illness of infancy and
childhood (80% of the cases are younger than 4 years) associated with an arteritis of
large to medium-sized arteries.
- Its significance stems in the involvement of coronary arteries, resulting MIs’.
- It may result from a delayed-type hypersensitivity response against cross reactive or
newly uncovered vascular antigen.
- Cytokine production and polyclonal B cell activation lead to the formation of
antibodies to endothelial cells and smooth muscle cells that precipitate the vasculitis. (
A variety of infectious agents, mostly viral, are thought to trigger the disease).

31. Morphology
- Resembles PAN, but with less prominent fibrinoid necrosis.
- The acute vasculitis typically subsides spontaneous or in response to
treatment, but aneurysm formation due to wall damage can
supervene.
- Healed lesions can exhibit obstructive intimal thickening.
- Pathologic changes outside the CVS are rarely significant.

33. Clinical Features
- It typically manifests with conjunctival and oral erythema and
blistering, edema of the hands and feet, erythema of the palms and
soles, desquamative rash and cervical lymph node involvement.
- 20% of untreated patients patients develop cardiovascular sequalae, ranging
from asymptomatic coronary arteritis, to coronary ectasia, to large coronary
aneurysms with rupture and thrombosis, MI, and sudden death.
- With IV immunoglobulin and aspirin, the rate of symptomatic coronary
artery disease is reduced to 4%

34. Microscopic
polyangiitis

35. Overview
- It’s a necrotizing vasculitis that generally effects capillaries as well as small arterioles and
venules.
- All lesions tend to be of the same age in any given patient.
- Skin, mucous membranes, lungs, brain, heart,GIT and kidneys can all be involved.
- Necrotizing glomerulonephritis (in 90% of patients) and pulmonary capillaritis are
particularly common.
- It can be a feature of a number of immune disorders such as Henoch-Schonlein purpura,
essential mixed cryoglobulinemia, or the vasculitis associated with CT disorders
- In some cases, Abs response to Ags have been implicated, which either lead to immune
complex deposition or secondary immune response, e.g.ANCAs developmeny, MPO-
ANCA in most cases.

36. Morphology

37. Clinical features
- They depend on the capillary bed that is involved and may include
hemoptysis, hematuria, proteinuria, abdominal pain and bleeding, muscle
pain or weakness and palpable cutaneous purpura.
- Immunosuppression and removal of the offending agent induce durable
remissions, with the exception of patients with widespread renal or CNS
involvement.

38. Wegener Granulomatosis

39. Overview
- It’s a necrotizing vasculitis characterized by the triad of findings:
- 1) Granulomas of the lung or upper respiratory tract.
- 2)Vasculitis of small to medium-sized vessels, most notably in the lungs
and URT.
- 3) Glomerulonephritis
- Limited forms can be restricted to the RT, while widespread forms can
affect eye, skin and other organs (notably the heart), and this resembles
PAN with the additional respiratory involvement features.
- It’s likely initiated by cell-mediated hypersensitivity response to an
inhaled infectious or environmental antigen.
- PR3-ANCAs are present in almost 95% of the cases and drive the
injurious reactions.

41. Clinical features
- The typical patient is a 40-year old man.
- Classic presentations include: Bilateral pneumonitis with nodules and
cavitary lesions, chronic sinusitis, renal disease and ulceration of the
nasopharynx ; with descending order.
- Renal involvement, if low-grade, will only cause hematuria and
proteinuria responsive to therapy, while severe renal involvement can
cause progressive renal failure.
- Nonspecific symptoms.
- Treatment with steroids, cyclophosphamides,TNF inhibitors and anti-B-
cell antibodies (Rituximab).

42. Churg-Strauss syndrome
(Allergic granulomatosis)

43. Overview
- It’s a small vessel necrotizing vasculitis, associated with asthma,
allergic rhinitis, lung infiltrates, peripheral eosinophilia, extravascular
necrotizing granulomas, and infiltration of vessels and perivascular
tissues by eosinophils.
- Cutaneous involvement, GIT bleeding and renal disease are the major
associations, also, cardiac involvement is seen in 60% of the cases and
is the major cause of morbidity and death.
- It might stem from hyperresponsiveness to some normally innocious
asllergic stimulus.
- MPO-ANCAs are present in a minority of cases.
- Presence of granulomas and eosinophils distinguishes the lesions
from those of PAN or Microscopic polyangiitis.

45. Buerger disease (Thromboangitis
obliterans)

46. Overview
- It’s characterized by focal acute or chronic inflammation of medium-
sized and small arteries, especially the tibial and radial arteries with
thrombosis, secondary extension into adjacent nerves and veins may
be seen.
- Occurs almost exclusively in heavy tobacco smokers, and usually
develops before 35.
- Unknown etiology, but direct toxicity and modification of vessel wall
components by reactive compounds in tobacco are suspected (most
patients with Buerger disease have hypersensitivity to tobacco
extracts).

48. Clinical features
- Early manifestations include cold-induced Raynaud phenomenon, instep
claudication and superficial nodular phlebitis.
- Pain usually accompanies the vascular insufficiency of Beurger disease,
undoubtedly from neural involvement.
- Chronic extremity ulcerations can develop, progressing overtime to frank
gangrene.

49. Vasculitis Associated with Other
Noninfectious Disorders
- Vasculitis resembling hypersensitivity angiitis or classic PAN can be
associated with many other disorders such as rheumatoid arthritis,
SLE, antiphospholipid antibody syndrome and Henoch-Schonlein
purpura.
- Rheumatoid vasculitis can occur in patients with severe, long-
standing cases of rheumatoid arthritis; it can cause aortitis but
typically affects small and medium arteries causing visceral
infarctions.

50. InfectiousVasculitis
- Localized arteritis can be caused by direct invasions of arteries by infectious
agents, usually Bacteria and Fungi, especially Aspergillus and Mucor spp.
- It can be part of more general tissue infection (bacterial pneumonia or
adjacent to abscesses) or –less commonly- by hematogenous spread during
septicemia or embolization from infective endocarditis.
- They can weaken the arterial walls and culminate in mycotic aneurysms, or
can induce thrombosis and infarctions
- Inflammation of vessels in bacterial meningitis can cause thrombosis and
infarction, leading ultimately to extension of a subarachnoid infection into
the brain parenchyma.