Vasculitis pathology Define and classify vasculitis. Describe the cause, pathogenesis, morphology, and clinical presentation of various types of vasculitis.

1. Objectives
Define and classify
vasculitis
Describe the cause ,
pathogenesis ,
morphology and clinical
presentation of various
types of vasculitis

2. Vasculitis
Vessel wall
inflammation
Pathogenesis
• Immune mediated
inflammation
• Direct invasion of vessel
wall by infectious pathology.

3. Non-
infectious
vasculitis
Cause – Local or systemic
immune response
Immunologic Injury is
caused by -
• Immune complex deposition
• Antineutrophil cytoplasmic
antibodies
• Antiendothelial antibody
• Autoreactive T cells

4. Antineutrophil Cytoplasmic
Antibodies (ANCAs)
• Heterogeneous group of autoantibodies
directed against
o neutrophil primary granules,
o monocyte lysosomes, and
o endothelial cells.
• ANCA associated vasculitis is
“pauci-immune” as vascular lesions do not
contain demonstrable antibody or
complement.
MCQ
SAQ

5. – Classified according to antigen specificity/
intracellular distribution of target antigen
– Anti-proteinase-3 (PR3-ANCA) / c -ANCA
• Neutrophil azurophilic granule constituent.
• trigerred by some infections
• Eg. Wegener granulomatosis/ Polyangitis
• Anti-myeloperoxidase (MPO-ANCA) / p-ANCA
– MPO is a lysosomal granule involved in generating
oxygen free radicals.
– induced by therapeutic agents- propylthiouracil
– Eg. Microscopic polyangiitis and Churg-Strauss
syndrome
ANCAs- MCQ’S ***

6. Antiendothelial
antibodies
Induced by
defects in immune
regulation
Eg. Kawasaki
disease

9. GIANT-CELL (TEMPORAL) ARTERITIS
• chronic, typically granulomatous
inflammation of large to small-
sized arteries.
• Most common form of vasculitis
• Elderly**, Rare before 50 years.
•
• Affects arteries in head
(temporal arteries-thickened,
nodular and tender) followed by
vertebral and ophthalmic
arteries.

10. GIANT-CELL
(TEMPORAL)
ARTERITIS..
C/F - vague and constitutional—
fever, fatigue, weight loss, facial
pain or headache
Giant-cell arteritis is a medical
emergency - prompt recognition
and treatment.
Ophthalmic arterial involvement
- permanent blindness

11. GIANT-CELL (TEMPORAL) ARTERITIS..
• Inflammatory lesions are segmental.
(biopsy -2- to 3-cm length of artery)
- nodular intimal thickening
- reduced luminal diameter.
• Classic lesions
- medial granulomatous inflammation that
leads to elastic lamina fragmentation.
- Multinucleated giant cells (75%)
Negative biopsy result does not exclude the
diagnosis

12. GIANT-CELL (TEMPORAL) ARTERITIS..

13. TAKAYASU ARTERITIS/ PULSELESS DISEASE
• Granulomatous vasculitis of medium and
larger arteries.
• Clinical features:
1. Ocular disturbances
2. marked weakening of pulses in upper
extremities.
• Age : less than 50 years **

14. TAKAYASU
ARTERITIS…
• Classically involves
• aortic arch
• – pulmonary A. , coronary and
renal arteries.
• Transmural irregular
• fibrous thickening of vessels with
intimal hyperplasia
• severe luminal
• narrowing of major branch vessels

15. Takayasu aortitis…
• Active disease:
destruction and
fibrosis of arterial
media associated with
mononuclear infiltrates ,
granulomatous inflammation
& giant cells
• Chronic – Collagenous
scarring with chronic
inflammatory cells.

16. Polyarteritis nodosa (PAN)
• Systemic vasculitis of medium or small-sized
muscular arteries.
• Typically involving renal and visceral vessels but
sparing the pulmonary circulation.
• ~ 30% of patients with PAN have chronic
hepatitis B and HBsAg is positive
– immune complex mediated etiology
• Types- Classic idiopathic PAN , Cutaneous PAN,
PAN associated with chronic hepatitis
MCQ

17. Polyarteritis
nodosa..
Typically Young adults.
Clinical features
- Malaise, fever, and weight loss
• Hypertension due to renal involvement
• Abdominal pain and malena
• Diffuse muscular aches and pains
• Peripheral neuritis
Therapy - corticosteroids and
cyclophosphamide

18. Polyarteritis nodosa..
• Morphology
• segmental transmural
necrotizing
inflammation of small to
medium-sized arteries
• affect only part of
vessel circumference.
• Vessels of kidneys,
heart, liver, and
gastrointestinal tract

19. Polyarteritis nodosa..
• Acute phase -
– transmural inflammation of arterial wall
– mixed infiltrate of neutrophils, eosinophils,
and mononuclear cells.
– fibrinoid necrosis
• Later phase -
- fibrous thickening of vessel wall.
• All stages of activity (early to late) coexist in
different vessels or within same vessel-
suggesting ongoing and recurrent insults.
MCQ

20. KAWASAKI
DISEASE/
Mucocutaneous
lymph node
syndrome
Acute febrile, self-limited illness of
infancy and childhood
arteritis affecting large to medium-
sized, and small vessels
Predilection for coronary artery
involvement - cause aneurysms -
rupture or thrombose - acute
myocardial infarctions

21. KAWASAKI
DISEASE…
Pathogenesis
unknown
infectious agents (viral) in triggering disease in
genetically susceptible.
Vascular damage is mediated by
activated T cells and monocytes /
macrophages

22. KAWASAKI DISEASE…
• Morphology –
– inflammation affecting entire thickness of
vessel wall
– fibrinoid necrosis is usually less prominent
• C/F –
– conjunctival and oral erythema and erosion
– edema of hands and feet
– erythema of palms and soles
– a desquamative rash
– cervical lymph node enlargement
(Mucocutaneous lymph node syndrome)

23. Microscopic polyangiitis/
hypersensitivity / leukocytoclastic vasculitis
Necrotizing vasculitis affecting capillaries,
arterioles and venules.
Necrotizing glomerulonephritis (90%) and
pulmonary capillaritis are common.
Skin, mucous membrane, lung, brain, heart, GIT,
kidney , Muscle- involvement
All lesions tend to be of same age are distributed
widely
MCQ

24. Microscopic polyangiitis- Pathogenesis
Antibody response to antigens – drugs
(Penicillin), micro-organisms(streptococci),
heterologous or tumour proteins.
Immune complex
deposition
recruitment & activation of
neutrophils within affected
vascular beds
Secondary immune
response – MPO ANCA
Clinical
manifestations-

25. Microscopic polyangiitis- Morphology
1. Segmental fibrinoid necrosis
of media
2. focal transmural necrotizing
lesions
3. granulomatous inflammation
is absent.
• Spare medium and larger
arteries- infarcts uncommon.
• In postcapillary venules only
infiltrating neutrophils, many
undergoing apoptosis-
leukocytoclastic vasculitis
• Little or no immunoglobulin
(“pauci-immune injury”).

26. Churg-Strauss
Syndrome /
Allergic
granulomatosis
and angitis
• Small-vessel necrotizing
vasculitis
• Associated with asthma,
allergic rhinitis, lung
infiltrates, peripheral
hypereosinophilia, and
extravascular necrotizing
granulomas.
• Mechanism : hyper
responsiveness to an
allergic stimulus in
patients with asthma
• Trigger : leukotriene
receptor antagonists

27. Churg-
Strauss
Syndrome…
Vascular lesions- segmental transmural
necrotizing inflammation , granulomas and
eosinophils.
MPO-ANCAs present (50%)
Multisystem diseases with -
• cutaneous involvement (palpable purpura),
• gastrointestinal tract bleeding
• renal disease (focal and segmental glomerulosclerosis)
• Myocardial involvement- cardiomyopathy

28. Wegener Granulomatosis/ Granulomatosis
with polyangitis
Necrotizing vasculitis characterized by –
• Necrotizing granulomas
of upper (ear, nose, sinuses, throat) or lower
respiratory tract (lung) or both
• Necrotizing or granulomatous vasculitis
small to medium-sized vessels of most
commonly lungs and upper airways
• Focal necrotizing, crescentic glomerulonephritis
MCQ

29. Wegener
Granulomatosis-
Pathogenesis
PR3-ANCAs (up to 95%)-
marker of disease activity,
prognosis and disease
pathogenesis.
T-cell–mediated hypersensitivity
response

30. Wegener Granulomatosis-
Morphology
• Upper respiratory tract lesions- Iinflammatory sinusitis
with mucosal granulomas to ulcerative lesions of nose,
palate, or pharynx, rimmed by granulomas with geographic
patterns of central necrosis and vasculitis
• Multiple granulomas coalesce to produce nodules in lung -
cavitate
• late stage - Granulomatous involvement of parenchyma and
alveolar hemorrhage
• Lesions may ultimately undergo progressive fibrosis and
organization.

31. Wegener’s granulomatosis…

32. Wegener Granulomatosis- Morphology
• Renal Lesions –
• Early : Glomeruli focal necrosism with isolated capillary
loop thrombosis (Focal and segmental necrotising
glomerulonephritis)
• Advanced: Diffuse necrosis with excuberant parietal
cell proliferation – cresent formation – (Cresentric
glomerulonephritis)

33. Wegener Granulomatosis- Clinical features
Males ~ 40 years
Pneumonitis with
bilateral nodular and
cavitary infiltrates
chronic sinusitis
mucosal ulcerations of
the nasopharynx
evidence of renal
disease

34. Behcet’s
disease
Small- to medium-vessel
neutrophilic
vasculitis
presents as a clinical triad of
recurrent oral aphthous
ulcers, genital ulcers, and
uveitis

35. Thromboangiitis Obliterans
(Buerger Disease)
Segmental,
thrombosing, acute and
chronic inflammation of
medium-sized and small
arteries,
tibial and radial arteries,
With secondary
extension into veins and
nerves of extremities
Leads to vascular
insufficiency of
extremities.
exclusively in heavy
cigarette smokers,
usually
before age 35

36. Vasculitis Associated with Other Noninfectious Disorders
Vasculitis resembling
hypersensitivity angiitis
or classic polyarteritis
nodosa
Rheumatoid arthritis-
Rheumatoid vasculitis
systemic lupus
erythematosus- Lupus
vasculitis
antiphospholipid
antibody syndrome
malignancy
Systemic illnesses-
mixed
cryoglobulinemia, and
Henoch-Schönlein
purpura.

37. Infectious
vasculitis
Direct invasion of
infectious agents-
Pseudomonas or fungi
Aspergillus and Mucor
species.
Mycotic aneurysms-
induce thrombosis and
infarction.