2. Vasculitis is a clinicopathologic process
characterized by inflammation and damage to
blood vessels, leading to compromise of the
vascular lumen resulting in ischemia of the
tissues supplied by the involved vessels.
3. Inflammatory destruction
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
4.
5. ANCA are antibodies directed against certain
proteins in cytoplasmic granules of
neutrophils and monocytes.
Types-i.
Cytoplasmic ANCA
ii. Perinuclear ANCA
6. Cytoplasmic ANCA
◦ Stains cytoplasm
(hence “c”)
◦ Main target antigen:
proteinase-3
◦ Associated with
wegner’s
granulomatosis
(Granulomatosis with
Polyangitis).
Perinuclear ANCA
◦ Stains perinuclear
(hence “p”)
◦ Main target antigen:
myeloperoxidase
◦ Associated with
churg strauss and
microscopic
polyangitis.
7.
8.
9. Granulomatous vasculitis of upper and lower
respiratory tracts with glomerulonephritis.
Mean age of onset-40 years
M:F= 1:1.
Histopathological hallmark-necrotizing
vasculitis of small arteries and veins with
granuloma formation.
14. Demonstration of necrotizing granulomatous
vasculitis on tissue biopsy.
Pulmonary tissue-highest diagnostic yield.
Renal biopsy-paauci-immune
glomerulonephritis.
Antibodies to cANCA-present in 90% pt with
active disease; without active disease
sensitivity is 60-70%.
15. Cyclophosphamide + Glucocorticoid- for induction of
therapy in severe disease.
Prednisolone 1mg/kg/d for 1st month f/b gradual
tapering on alternate day or daily schedule with
discontinuation after 6-9 months.
Cyclophosphamide 2mg/kg/d orally for 3-6 months.
Remission maintanence-
• Methotrexate 0.3 mg/kg single weekly (max 15 mg/week)
• Azathioprine 2mg/kg/d
• Mycophenolate mofetil- 1000 mg bd
Maintanence therapy given for min 2 years.
16. On t/t with cyclophosphamide
• marked improvement is seen in >90% patient;
• complete remission in 75% patient;
• 5 year patient survival is >80%.
17. It is a systemic necrotizing vasculitis without
immune globulin deposition (pauci-immune) that
affects mainly small vessels.
Glomerulonephritis and pulmonary capillaritis is
common.
No granuloma formation.
Mean age of onset- 57 years.
M>F
19. Onset may be gradual- fever, weight loss and
musculoskelatal pain.
Glomerulonephritis (79%)-can be rapidly
progressive leading to renal failure.
Alveolar haemorrhage (12%)- haemoptysis.
Mononeuritis multiplex, GI tract and
cutaneous vasculitis.
20. Lab Findings-
ESR- raised
Anaemia
Leukocytosis
Thrombocytosis
ANCA- present in
75%
(antimyeloperoxida
se antibodies)
21. Based on histologic evidence of vasculitis or
pauciimmune glomerulnephritis.
Sensitivity and specificity of ANCA is not
established.
23. Also referred to as allergic angiitis and
granulomatosis.
characterized by asthma, peripheral and
tissue eosinophilia , extravascular granuloma
formation, and vasculitis of multiple organ
systems.
Incidence-uncommon (1-3/million)
Mean age- 48 years
M:F- 1.2:1.
24. Involves small and medium-sized muscular
arteries, capillaries, veins, and venules.
characteristic histopathologic feature-granulomatous
reactions associated with
infiltration of the tissues with eosinophils.
Lung involvement is predominant.
25. Nonspecific-Fever, malaise,anorexia, and
weight loss.
Pulmonary finding-M/C manifestation
Severe asthmatic attacks with pulmonary
infiltration.
Mononeuritis multiplex-2nd most common
manifestation.
Allergic rhinitis and sinusitis-61%
Heart disease-14% ;important cause of
mortality (CHF or Heart attack).
26. Skin lesions occur in 51% of patients and
include purpura in addition to cutaneous and
subcutaneous nodules.
The renal disease is less common and
generally less severe.
28. The characteristic finding-eosinophilia.
Evidence of inflammation-elevated ESR,
fibrinogen, or α2-globulins
48% of patients have circulating ANCA that is
usually antimyeloperoxidase(pANCA).
29. Lanham’s criteria (all of the following)
◦ Asthma
◦ Peak eosinophilia >1.5 x 109 cells/L
◦ Systemic vasculitis, two or > extrapulmonary sites
American College of Rheumatology (4 of the
following in the setting of vasculitis)
◦ Asthma
◦ Peak eosinophilia >10% total WBC
◦ Peripheral neuropathy attributed to vasculitis
◦ Transient pulmonary infiltrates
◦ Paranasal sinus disease
◦ Biopsy showing blood vessels with extravasular
eosinophils
30. Glucocorticoids -oral prednisolone 40-60
mg/day.
In glucocorticoid failure/fulminant
multisystem disease, the treatment of choice
is a combined regimen of daily
cyclophosphamide and prednisolone.
Prognosis-
Without t/t-25%
With t/t-72%
31.
32. Multisystem, necrotizing vasculitis of small
and medium sized muscular arteries.
Renal and visceral arteries are
characteristically involved.
Uncommon.
33. Necrotizing inflammation of small and
medium sized muscular arteries.
Lesions are segmental and involve bifurcation
and branching of arteries.
Aneurysmal dilatation of upto 1cm along
involved arteries is characteristic.
Pulmonary arteries are not involved; bronchial
artery involvement is uncommon.
37. Lab findings-
• Leukocyte counts is raised with neutrophil
predominance.
• Raised ESR
• Anaemia of chronic disease.
• Hypergammaglobulinemia.
• All patients must be screened for Hep B.
38. Severe Cases-Prednisolone +
Cyclophosphamide
Less Severe- Prednisolone alone.
Patient with Hepatitis B- Antiviral therapy
with glucocorticoids and plasma exchange.
Prognosis-o
Without t/t-5 year survival rate is 10-20%.
o Death is mainly b/s of GI complications and
cardiovascular causes.
39.
40. Cranial arteritis or temporal arteritis.
Inflammation of medium and large sized
arteries.
Characteristically involves one or more
branches of carotid artery-temporal artery.
41. It is closely assoc with polymyalgia
rheumatica which is characterized by
stiffness, aching and pain in muscle of neck,
shoulder, lower back, hips and thigh.
Occurs in >50 years of age.
F>M
Has association with HLA-DR4.
42. Histopathologically- panarteritis with
inflammatory mononuclear cell infiltrate with
giant cell formation.
Antigen driven disease-activated T-lymphocytes,
macrophages and dendritic
cells.
43. Fever, anemia, high ESR and headache.
Malaise, fatigue, anorexia, weight loss,
sweats, arthralgia, polymyalgia rheumatica.
Headache with tender thickened and nodular
artery.
44. Scalp pain, claudication of jaw and tongue.
Ischemic optic neuropathy- most feared
complication.
Stroke, scalp or tongue infarction.
Arm claudication, aortic aneurysm.
Lab Findings-
• Raised ESR.
• Normochromic or slightly hypochromic anemia.
• Increased levels of IgG and complements.
45. Confirmed by biopsy of temporal artery.
Segmental involvement-biopsy of 3-5 cm
together with serial sectioning of biopsy
specimen.
Large vessel disease- suggested by physical
examination and confirmed by vascular
imaging.
46. Glucocorticoids- Prednisone 40-60 mg/d for
1 month f/b gradual tapering.
Ocular involvement-methylprednisolone
1000 mg/d for 3 days.
Treatment required for >2 years.
Aspirin 81 mg/d-reduce cranial ischemic
complication.
Patient with isolated polymyalgia rheumatica-prednisone
at lower dose.
ESR- for monitoring of therapy.
47. Inflammatory and stenotic lesion of medium
and large sized arteries.
It has strong predilection for aortic arch and
its branches.
Incidence- 1.2-2.6 cases/million.
Adolescent girls and young women.
48. Medium and large arteries.
Panarteritis with inflammatory mononuclear
cell infiltrate.
Immunopathogenic mechanism.
49. Malaise, fever, night sweats, arthralgia, anorexia
and weight loss.
Subclavian (93%)- arm claudication, raynaud’s
phenomena
Common carotid (58%)- syncope, TIA, stroke.
Abdominal aorta (47%)- abdominal pain,
nausea,vomiting.
Renal (38%)- hypertension, renal failure.
51. Suspect in young women with decreased or
absent peripheral pulses, discrepencies in BP
with arterial bruits.
Diagnosis confirmed by- arteriography which
shows– irregular vessel wall, stenosis, post
stenotic dilatation, aneurysm formation,
occlusion with increased collateral circulation.
52. Arteriogram demonstrating
stenosis of the abdominal
Aorta.
Arteriogram of the aortic arch
demonstrating complete
occlusion of the left common carotid
artery just after its origin
from the aorta.
53. Chronic and relapsing course.
Prednisone 40-60 mg/d alleviates symptoms.
Glucocorticoids therapy with surgical or
arterioplastic approach– improved outcome.
Refractory to glucocorticoid- methotrexate
25mg/week.
Mortality- CHF, MI, CVA, aneurysmal rupture or
renal failure.
54.
55. Also k/a anaphylactoid purpura.
Small vessel vasculitis.
Palpable purpura, arthralgias, GI signs and
symptoms and glomerulonephritis.
Children-4-7 years.
Common.
M:F- 1.5:1
Peak incidence in spring.
57. Palpable purpura
Polyarthralgia
Colicky abdominal pain with nausea, vomting,
diarrhoea or constipation accompanied by
passage of blood and mucus per rectum.
Bowel intussusception.
Renal (10-50%)- mild glomerulonephritis-proteinuria
and microscopic hematuria with
rbc cast.
58.
59. Lab studies-
mild leukocytosis, normal platelet count
Skin biopsy- leukocytoclastic vasculitis with
IgA and C3 deposition.
60. Prednisone 1mg/kg/d-useful in decreasing
tissue oedema, arthralgias and abdominal
discomfort.
Rapidly progressive glomerulonephritis-intensive
plasma exchange with cytotoxic
drugs.
Prognosis- excellent.
61. Cryoglbulins are cold precipitable monoclonal
or polyclonal immunoglobulins
Idiopathic or associated with disorders like
multiple myeloma, lymphoproliferative
disorder, connective tissue diseases,
infections and liver diseases.
Hepatitis C is commonly related with it.
62. Skin biopsy- inflammatory infiltrate
surrounding and involving blood vessel walls
with fibrinoid necrosis, endothelial cell
hyperplasia and haemorrhage.
Membranoproliferative glomerulonephritis is
responsible for 80% of all renal lesions.
64. Glomerulonephritis- poor prognostic sign
15% end stage renal disease.
Hepatitis C infection- IFN-α and ribavarin.
Glucocorticoids- transient response.
Plasmapheresis, cytotoxic agents- carry
significant risk.
65. Also called as Primary angitis of CNS.
vasculitis restricted to vessels of CNS without
other systemic vasculitis.
Mononuclear cell infiltrate with or without
granuloma formation.
Headache, altered mental function and focal
neurological deficit.
Systemic symptoms are absent.
66. Diagnosis-
MRI Brain.
Arteriography
Cerebral arteriogram demonstrating
beading alongbranches of the internal
carotid artery
67. Confirmed by biopsy of brain parenchyma
and leptomeninges.
Poor prognosis
Treatment-glucocorticoid
± cyclophosphamide.
