Vasculitis refers to inflammation of blood vessels. This document discusses the classification, pathogenesis, and syndromes of vasculitis. It is difficult to classify vasculitis due to overlapping features and unknown causes. The Chapel Hill system divides vasculitis by vessel size. Mechanisms include immune complex formation, ANCA production, and T-cell responses. Large vessel vasculitis includes giant cell arteritis and Takayasu arteritis. Giant cell arteritis causes headaches and vision loss. Treatment is glucocorticoids. Takayasu arteritis causes reduced pulses and organ ischemia, especially in young Asian women. Both can lead to complications like aneurysms if untreated.

1. VASCULITIS
TAJUL NISA AJLA
IMS Bangalore, 2016

2. INTRODUCTION
• DEFINITION:
– Clinicopathologic process characterized by inflammation of and
damage to blood vessels- tissue ischemia of affected vessel
• Have diverse clinical feature and group of syndromes since its
involvement in any type, size, and site of vascular beds. Clinical
feature also include constitutional symptoms.
• Can present as a sole manifestation (primary)
• May be a secondary component of another disease.
• Can be confined to a single organ or involve several organs

3. CLASSIFICATION
• Overlapping and lack of understanding of the pathogenesis
of vasculitis syndrome has made vasculitis difficult to classify.
• Various classification schemes are attempted; based on
vessel size, role of immune complex, presence of specific
antibody, granuloma formation and organ specificity.
• Chapel Hill nomenclature has been used in organizing this
diverse group of entities
– By dividing the disease based on size of vessel

4. Chapel Hill

5. VASCULITIS SYNDROMES

6. PATHOGENESIS
Immune complex formation
ANCA
Pathogenic T-lymphocyte response

7. Pathogenic immune-
complex formation
and/or deposition
• IgA vasculitis (Henoch-
Schönlein)
• Lupus vasculitis
• Serum sickness and
cutaneous vasculitis
syndromes
• Hepatitis C virus–
associated
cryoglobulinemic
vasculitis
• Hepatitis B virus–
associated vasculitis
Production of ANCA
• Granulomatosis with
polyangiitis (Wegener’s)
• Microscopic polyangiitis
• Eosinophilic
granulomatosis with
polyangiitis (Churg-
Strauss)
Pathogenic T lymphocyte
responses and
granuloma formation
• Giant cell arteritis
• Takayasu arteritis
• Granulomatosis with
polyangiitis (Wegener’s)
• Eosinophilic
granulomatosis with
polyangiitis (Churg-
Strauss)
Potential Mechanisms of Vessel Damage in
Vasculitis Syndromes

8. IMMUNE COMPLEX MECHANISM
• Damage to the vessel wall is due to deposition of
immune complex, but the cause of immune complex
formation is not clearly establish
• The actual antigen in the immune complex is rarely
identified
• In Polyarteritis nodosa, hepatitis B antigen is found in
both circulating and deposited immune complexes.
• In cryoglobulinemic vasculitis, hepatitis C has been
identified in the cryoprecipitate of the pts.
• The mechanism of of tissue damage resembles serum
sickness, type 3 hypersensitivity reaction.

10. ANTINEUTROPHIL CYTOPLASMIC
ANTIBODIES (ANCA)
• ANCA is autoantibodies that is directed against certain
protein in cytoplasmic granules of neutrophils and
monocyte
• ANCA was found in:
– Granulomatous polyangiitis (Wegener’s)
– Microscopic polyangiitis
– Eosinophilic granulomatous polyangiitis (Churg-Strauss)
• These disease are grouped as “ANCA-associated vasculitis”

11. Two category of ANCA:
cytoplasmic ANCA
(cANCA): proteinase-3
antigen
Perinuclear ANCA
(pANCA): enzyme
myeloperoxidase

13. PATHOGENIC T-LYMPHOCYTE RESPONSE
AND GRANULOMA FORMATION
• Histopathologic feature of granulomatous
vasculitis shows there is role of pathogenic T
lymphocyte response and cell mediated injury

14. Endothelial cells express HLA
class 2 molecule following
activation by cytokines; INF ƴ
Act like APC; interact with CD+4
T cells
Endothelial cell secrete IL
Activate the T cell and cause
immunologic process within the
blood vessel
IL-1 and INF-α are potent inducer of:
• endothelial-leucocyte adhesion
molecule 1 (ELAM-1)
• vascular cell adhesion molecule 1
(VCAM-1)
These enhance the adhesion of
leucocytes to endothelial cell

15. APPROACH TO THE
PATIENT

16. Diagnosis
• Unexplained systemic illness
• Palpable purpura
• Pulmonary infiltrates
• Microscopic hematuria
• Chronic inflammatory sinusitis
• Mononeuritis multiplex
• Unexplained ischemic event
• Glomerulonephritis with evidence of multisystem
disease
*Exclude other disease that mimic vasculitis

19. Infectious diseases
• Bacterial
endocarditis
• Disseminated
gonococcal infection
• Pulmonary
histoplasmosis
• Coccidioidomycosis
• Syphilis
• Lyme disease
• Rocky Mountain
spotted fever
• Whipple’s disease
Coagulopathies/thrombotic
microangiopathies
• Antiphospholipid
syndrome
• Thrombotic
thrombocytopenic
purpura
Drug toxicity
• Cocaine
• Levamisole
• Amphetamines
• Ergot alkaloids
• Methysergide
• Arsenic
Antiglomerular basement
membrane disease
(Goodpasture’s syndrome)
Neoplasms
Atrial myxoma
Lymphoma
Carcinomatosis
Atheroembolic disease
Migraine Amyloidosis
CONDITION THAT MIMIC VASCULITIS

20. LARGE VESSEL ARTERITIS:
GIANT CELL ARTERITIS (TEMPORAL)
TAKAYASU ARTERITIS

21. GIANT CELL ARTERITIS
• Historically referred to as temporal arteritis
• Chronic granulomatous inflammation of medium and
large arteries
• Involves one or more branches of carotid artery;
temporal artery,
• Systemic disease affect aorta and its branches,
• Can also involves vertebral arteries ophthalmic artery,
aorta

22. • Closely associated with polymyalgia rheumatica
– Stiffness, aching, and pain in the muscle of neck, shoulder,
lower back, hips, and thighs.
– Polymyalgia usually occurs as an isolation, 40-50% is
associated with giant cell arteritis, 10-20% pt presented
with polymyalgia may develop giant cell arteritis later
GIANT CELL ARTERITIS

23. • Age > 50 years
• Common more in women, rare in blacks
• High incidence in Scandinavia and region in US with
large population of Scandinavians
• Familial aggregation; association with HLA-DR4.
• Genetic studies shows association of giant cell arteritis
with alleles at HLA-DRB1 locus,
GIANT CELL ARTERITIS; INCIDENCE
AND PREVALENCE

24. PATHOLOGY
• Panarteritis, multiple arteries
are involved
• Histopathology: inflammatory
mononuclear cell infiltrates
within vessel wall with frequent
giant cell formation
• Proliferation of intima and
fragmentation of internal elastic
lamina
• Often cause ischemia of affected
organs.

25. PATHOGENESIS
• T-cell mediated immune response against an
unknown vessel wall antigen
• T-lymphocytes, dendritic cells, and
macrophages plays a critical role in disease
pathogenesis.

26. CLINICAL MANIFESTATION
• Constitutional symptoms:
– Fever, malaise, myalgia, night sweats, weight loss
• Hallmark symptom:
– New onset of localized headache; temporal area,
diffuse, bilateral
• Cranial artery symptoms:
– Headache, tender, thickened or nodular artery,
pulsatile but may occlude later, scalp pain,
claudication of jaw and tongue

27. CLINICAL MANIFESTATION
• Ophthalmic manifestations: ischemic optic
neuropathy
– Visual blurring, transient blurring, diplopia, eye
pain, sudden loss of vision
• Polymyalgia Rheumatica:
– Fever, malaise, pain and stiffness of neck,
shoulder, hip muscle without any abnormalities in
physical examination

28. CLINICAL MANIFESTATION
• Large vessel manifestation:
– Subclavian artery stenosis- arm claudication
– Aortic aneurysm; thoracic, abdominal aorta lead
to rupture and dissection
• LAB FINDING:
– Elevated ESR, normochromic or hypochromic
anemia, increased IgG and complement
– Alkaline phosphatase

29. DIAGNOSIS
• >50 yrs old pt with fever, anemia, high ESR
• With or without symptom of polymyalgia
rheumatica
• Diminish pulse, bruit
• Ocular signs and symptom
• Biopsy of temporal artery, ultrasound, and
arteriogram

30. TREATMENT OF GAINT CELL ARTERITIS
• Goal of treatment: Reduce symptom, prevent
visual loss
• Glucocorticoid;
– Prednisone: 40-60 mg/d for one month, gradual
tapering
– Methylprednisolone: 1000 mg daily, for 3 days, if
ocular sign occurs
– Level of ESR can be a guide while tapering the dose of drugs
• Aspirin, 81 mg daily to reduce risk of cranial
ischemia
• Tocilizumab (anti IL 6 receptor)- need further
study

31. COMPLICATION
• Fatality due to:
– Cerebrovascular disease
– Myocardial infarction
– Aortic aneurysm rupture
– dissection

32. TAKAYASU ARTERITIS
• DEFINITION:
– Inflammation and stenotic disease of medium and
large-sized arteries
– Have strong predilection for the aortic arc and its
branches, may also involve pulmonary artery
• Uncommon disease
• Adolescent girls and young women, more
common in Asia

33. PATHOLOGY AND PATHOGENESIS
• Large and medium-sized artery; panarteritis
• Immunopathogenic mechanism; demonstration of
circulating immune complex
• Marked intimal proliferation, fibrosis, scarring,
vascularisation of media, disruption and degeneration
of elastic lamina.
• Narrowing of lumen occurs with or without thrombosis
• Involve vasa vasorum
• Compromised blood flow- ischemia

34. CLINICAL FEATURE
• GENERALISED SYMPTOM: malaise, fever, night
sweats, arthralgia, anorexia, weight loss
• Vascular symptom: absent peripheral pulse
(subclavian artery), organ ischemia
• Hypertension- contributes to renal, cardiac,
cerebral injury
• LAB FINDING: elevated ESR, anemia, elevated
immunoglobulin

35. DIAGNOSIS
• Young women, with decrease or absence of peripheral
pulse, discrepancies in BP, arterial bruit.
• Arteriography: irregular vessel wall, stenosis,
poststenotic dilation, aneurysm, occlusion, increased
collateral circulation
• MRA, complete aortic arteriography by catheter-
directed dye arteriography- to delineate the
distribution and degree of arterial disesase

36. • HISTOPATHOLOGIC:
– vessel wall inflammation
– predominant lymphocytic with granuloma
formation
– giant cell at vessel wall
– lymphoplasmacytic infiltrate rich in IgG4-positive
plasma cells, storiform.
– Fibrosis, obliterative phlebitis.
DIAGNOSIS

37. TREATMENT TAKAYASU ARTERITIS
• Glucocorticoids:
– Prednisone; 40-60 mg per day- alleviate symptoms
• Surgical and arterioplastic approach to
stenosed vessels: decrease risk of stroke,
improving blood flow to ischemic viscera and
limbs
• Methotrexate up to 25 mg per week
• Anti-TNF- need further study

38. COMPLICATION
• Death occur due to:
– Congestive cardiac failure
– CVA
– MI
– Aneurysm rupture
– Renal failure
• Chronic and relapsing

39. REFERENCE
• Harrison's Principle of Internal Medicine 19th Edition
• Davidson’s Principles & Practice of Medicine 22nd
Edition

40. THANK YOU