2. Vasculitis is a heterogeneous group of disorders
characterized by inflammatory destruction of
blood vessels
Inflamed blood vessels are liable to occlude,
rupture or develop a thrombus leading to
ischemia of tissues and organs supplied by the
vessel
Because of multivessel involvement, it begins
with non specific symptoms and has tendency to
affect multiorgans
Involves immunological mechanisms and can
result in variety of presentations depending upon
the type and size of the vessel involved
3. Can affect all ages although some are restricted to
particular age groups
More common in caucasians
Constitutional symptoms like malaise, fever, fatigue
and loss of appetite are common in the beginning of
disease
Chronic relapsing disease having phases of waxing
and waning
Takayasu arteritis is most common in Indian setup
Has a typical subacute course unfolding over weeks
to months and often the patient is unable to recall
the exact time when the disease began
Symptoms and signs of inflammation are striking and
include fever, arthritis, rash, etc.
Pain is a common manifestation originating from the
organ involved
4. It can be:
1. Primary i.e. vasculitis is the principal
feature
2. Secondary i.e. secondary to external
stimuli
Drugs : hydralazine, phenytoin, allopurinol
etc
Infections : SABE, EBV, HIV
Collagen disorders like RA, SLE, scleroderma
Malignancies like hairy cell leukemia.
5. DOMINANT
VESSEL
PRIMARY VASCULITIS PATHOGENESIS SECONDARY
VASCULITIS
LARGE ARTERIES TEMPORAL ARTERITIS
TAKAYASU ARTERITIS
T cell mediated ASSOCIATED WITH
RA, SYPHILLIS, TB
MEDIUM ARTERIES CLASSICAL PAN
KAWASAKI DISEASE
IMMUNE COMPLEX
RELATED
ANTIBODY MEDIATED
HYPERSENSITIVITY
HBV ASSOCIATED
PAN
SMALL AND
MEDIUM SIZED
WEGENER’S
GRANULOMATOSIS
CHURG STRAUSS
SYNDROME
MICROSCOPIC ANGITIS
ANCA MEDIATED ASSOCAITED WITH
DRUGS, HIV,
INFECTIONS LIKE
HIV
SMALL VESSEL
VASCULITIS
HSP
EMC
IMMUNE COMPLEX
MEDIATED
HCV INDUCED,
DRUGS
6.
7. IMMUNE COMPLEX MEDIATED – PAN, EMC ,HSP
Deposition of immune complexes in vessel wall
activation of complements destruction of vessel wall
ANCA MEDIATED: WG, CSS, MPA
Aberrant expression of antigens over the surface of
neutrophils formation of antibodies destruction of
neutrophils vessel wall damage
T LYMPHOCYTE RESPONSE AND GRANULOMA
FORMATION – WG, GCA, TA
Delayed hypersensitivity and cell mediated immune injury
leading to granuloma formation
8. Antibodies directed against neutrophil granule
constituents
C-ANCA
stains cytoplasm in diffuse granular pattern
Main target is proteinase-3
Highly specific for WG
P-ANCA
stains perinuclear or nuclear matter in peculiar
pattern
Main target is myeloperoxidase
a/w MPA and CSS
9.
10. Unexplained signs and symptoms
Multisystem involvement
High ESR and CRP
Skin lesions like palpable purpura, livedo
reticularis
Sudden vision loss / headache
Arthralgias and myalgias
Ischemic changes like Raynaud's gangrene,
claudication
Mononeuritis multiplex
Pulmonary infiltrates
Microscopic hematuria
Absence of pulses, presence of bruits
11. LARGE VESSELS
AORTA AND ITS
MAJOR BRANCHES
MEDIUM VESSELS
VISCERAL ARTERIES
MUSCULAR ARTERIES
SMALL VESSELS
INTRAPARENCHYMAL
ARTERIES ATERIOLES
CAPILLARIES
LIMB CLAUDICATION ULCERS PURPURA
ASSYMETRIC BLOOD
PRESSURE
LIVEDO RETICULARIS URTICARIA
ABSENCE OF PULSES DIGITAL GANGRENE GLOMERULONEPHRITIS
BRUITS MONONEURITIS
MULTIPLEX
ALVEOLAR
HAEMORRHAGE
AORTIC DILATATION MICROANEURYSM SPLINTER
HAEMORRHAGE
RENOVASCULAR
HYPERTENSION
UVEITIS EPISCLERITIS
SCLERITIS
12.
13. Temporal arteritis/cranial arteritis
Principally involves extracranial branches of common
carotid artery
More common in women above the age of 50
Headache >2/3 cases d/t temporal artery
involvement and is new or different
Scalp tenderness with nodular/thickened artery
Most dreaded complication is irreversible blindness
d/t AION
Jaw claudication pain while eating
POLY MYALGIA RHEUMATICA (40-50% cases stiffness in
neck, shoulder, hip)
Mortality is low and due to CVA, aortic aneurysms
Treatment is done with steroids
14. ACR 3/5 Diagnostic criteria
Age>50
New onset headache
Abnormal temporal artery
ESR >50mm/hr
Granulomatous inflammation with multinucleate
giant cells on biopsy of temporal artery
15. Large vessel granulomatous arteritis aka
pulseless disease/aortic arch syndrome
Involves aorta and its branches
Transmural involvement is present on histology
involving all the three layers of vessel
More common in woman in reproductive
years(manifests below the age of 40)
Subclavian vessels and aortic arch most
commonly involved
Shares many attributes with giant cell arteritis
but the latter is more common in females above
the age of 40 yrs
Diagnosis is made by arteriography
16. 3/6 AMERICAN COLLEGE OF RHEUMATOLOGY
AGE<40 YRS
CLAUDICATION OF EXTREMITIES
DECREASED BRACHIAL ARTERY PULSE
>10mm Hg DIFFERENCE IN SBP OF ARMS
BRUIT OVER SCA/AORTA OR ITS BRANCHES
ARTERIOGRAPHIC EVIDENCE OF NARROWING OF AORTA
Artery Clinical features
Subclavian(93%) Arm claudication, Raynaud’s phenomenon
Common carotid(58%) Visual disturbances, TIA
Abdominal aorta(47%) Abdominal pain, nausea
Renal(38%) Hypertension, renal failure
Vertebral Visual changes, dizziness
Iliac Leg claudication
Coronary Chest pain, angina, MI
17. It is divided into 5 types according to the
territory of aorta involved
TYPE I involves aortic arch and its branches
TYPE II involves aorta at its ascending portion
TYPE III involves aorta at its descending portion
TYPE IV sole involvement of abdominal aorta
TYPE V generalised involvement of all segments
of aorta
Treatment is with steroids in acute cases and
with surgery in chronic cases
Prognosis is good and death is rare and if it
occurs it is d/t CHF, CVA, MI
18.
19.
20. Acute febrile illness of infants and children
<5 yrs
Referred to as mucocutaneous lymph node
syndrome
Vasculitis of coronary arteries is the most
dreaded complication occurs during 3rd to 4th
week
Treatment is done with IVIG and aspirin
The prognosis is good and most of the
patients recover uneventfully
23. Vasculitis of medium to small sized muscular arteries,
renal and visceral arteries with sparing of pulmonary
circulation which differentiates it from AAV vasculitis
Transmural inflammation and segmental involvement
Musculoskeletal>renal>skin>git
Renal involvement leading to renin mediated
hypertension without causing glomerulonephritis
Digital gangrene and livedo reticularis in the skin
Absence of ANCA or pulmonary involvement
Aneurysmal dilatation up to 1cm along vessels
Association with hepatitis B virus in 30% cases
Prognosis is poor in untreated cases and death occurs
d/t bowel infarcts, perforation, CVS involvement
24. DIAGNOSIS CRITERIA BY ACR 3/10
WEIGHT LOSS>4KG
LIVEDO RETICULARIS
TESTICULAR PAIN
MYALGIAS/WEAKNESS OF LEG MUSCLES
MONO/POLYNEUROPATHY
DIASTOLIC BP >90mm Hg
ELEVATED BUN/CREATININE
HEPATITIS B VIRUS
ARTERIOGRAPHIC ABNORMALITIIES
BIOPSY OF THE ARTERY SHOWING POLYMORPHS
25.
26.
27. Granulomatous vasculitis of small vessels and
venules involving respiratory tract
H/o prior asthma/nasal polyp/allergic rhinitis is
present
It is non destructive which distinguishes it from
WG
Diagnosis by 4/6 criteria by American college of
rheumatology
Asthma
Mono/polyneuropathy
Eosinophilia
Pulmonary infiltrates
Extravascular eosinophils
Paranasal sinus abnormality
28. Elevated serum IgE and Eosinophils
Cardiac involvement in form of CHF in 12.5%
of cases
Migratory pulmonary infiltrates on chest x-
ray in 1/3 pts
P-ANCA +ve in 70% cases
More responsive to steroids alone
Prognosis in untreated cases is poor but
improves with treatment death occurs d/t
cardiac involvement
29. Anaphylactoid purpura involves small vessels
and post capillary venules in GIT, SKIN,
JOINTS. It is characterized by tetrad of:
1. Palpable purpura concentrated over buttocks
and lower limbs and occurs in crops
2. Migratory arthralgias involving large joints of
lower limbs and is non deforming
3. Abdominal pain is colicky and worsens after
eating ; can lead to intussception
4. Glomerulonephritis appears after skin
involvement and l/t microscopic hematuria
30. mean age is 5 years
Skin manifestations and arthralgias are more
common in adults
Serum IgA levels are elevated in 60% pts with
normal complement levels
Skin biopsy shows leukocytoclastic vasculitis
with IgA and C3 deposition
Proteinuria and hematuria are common
Excellent prognosis with very low mortality
Treatment is with steroids
31.
32. Small vessel granulomatous vasculitis
characterized by triad of:
Acute necrotizing granuloma of URT/LRT
Necrotizing or granulomatous vasculitis of small
to medium arteries
Renal disease in form of glomerulonephritis
Nasal/sinus disease (90%)of young and middle
age can lead to septal perforation
Mean age of onset is about 40 yrs with M:F=
1:1
Both conductive and sensorineural hearing
loss can occur
33. Nasal/oral ulcers purulent/bloody discharge and
produce characteristic appearance known as
strawberry gingivitis
Renal glomerulonephritis follows respiratory
involvement and can progress rapidly
On chest x-ray lesions like nodules, infiltrates,
cavities are seen
Chronic nasal carriage of staph aureus is associated
with high relapse rate
Prognosis is poor and death occurs d/t renal disease
C-ANCA +VE in 90% cases
Urine exam’n reveals abnormal urine
sediments(microhematuria, RBC casts)
Open biopsy from lung is more specific
Treatment is with glucocorticoids and cytotoxic
agents
34.
35. Non granulomatous necrotizing small vessel
vasculitis affecting arterioles, capillaries and
venules
More common in aged males (>50 yrs)
Kidneys>>joints>>skin>>lungs>>peripheral nerves
Pauciimmune glomerulonephritis
Migratory polyarthritis which is non destructive
Persistent cough with /without hemoptysis d/t
pulmonary capillaritis l/t alveolar haemorrhage
Purpura of skin and mononeuritis multiplex
It should be differentiated from
Wegeners- presence of granulomas and is destructive
PAN- no pulmonary involvement, ANCA –ve, no
glomerulonephritis hypertension is common
36. Most commonly encountered vasculitis aka
hypersensitivity vasculitis
Etiology is drug allergy or chronic urticaria
Dermal small vessel vasculitis with leucocytoclasis
leading to palpable purpura which may be painful
with burning sensation and edema
Lesions are common on dependent parts
Post capillary venules are most commonly involved
DIAGNOSIS BY ACR 5 FEATURES
AGE>16 YRS AT ONSET
MEDICATION AT ONSET AS A PRECIPITATING FACTOR
PALPABLE PURPURA
MACULOPAPULAR RASH
BIOPSY SHOWING GRANULOCYTES AROUND ARTERIOLES
AND VENULES
37. Cryoglobulins are mono/polyclonal ig that
precipitate at<37 C and redissolve on warming
Characterized by palpable purpura, arthralgia,
neuropathies and glomerulonephritis
Small vessel vasculitis d/t deposition of immune
complexes
Associated with chronic hepatitis C, multiple
myeloma and lymphoproliferative disorders
Rheumatoid factor is present in almost all cases
Pulmonary, renal(MPGN), cutaneous vasculitis,
polyarthralgias
43. First the disease mimicking vasculitis should
be excluded.
HEMOGRAM usually shows:
NCNC anemia
Leukocytosis
Eosinophillia (>10% in CSS)
ACUTE PHASE REACTANTS like:
CRP, alpha 2 globulin, fibrinogen and ESR are
raised.
44. URINE EXAMINATION
Hematuria/proteinuria
SERUM PROTEINS
Complementary levels are reduced
Hypergammaglobinemia (mostly IgG type)
ANCA
C – ANCA, p – ANCA
45. ORGAN BIOPSY -
Temporal artery – GCA
Pulmonary tissue – small vessel vasculitis
Upper airway – wegeners
Renal biopsy –
RPGN in pauciimmune MPA
MPGN in EMC
SKIN BIOPSY in leukocytoclasis in cutaneous vasculitis
47. DEPENDS UPON THE TYPE SEVERITY AND RATE OF
PROGRESSION OF DISEASE
Treatment options include:
GLUCOCORTICOIDS
GLUCOCORTICOIDS + CYTOTOXIC DRUGS
IVIG OR ASPIRIN
ANTIVIRAL THERAPY (if indicated)
SURGICAL CORRECTION AND ANGIOPLASTY
NEWER ADVANCES
WBC COUNT to be repeated every 1-2 wks and
maintained above 3000/microL
TMP-SMX prophylaxis to patients receiving
steroids + cytotoxic drug combination therapy
49. INDICATIONS & DOSE
Severe ulcerative and necrotic lesions
Acute glomerulonephritis
Treatment of choice in CSS, TA, GCA
Dose is 1mg/kg/d x 1 month f/b alternate day
and then tapered further
Discontinue in 6-9 months
SIDE EFFECTS
Osteoporosis, cataract, diabetes, myopathy, AVN,
psychosis
50. CYCLOPHOSPHAMIDE
INDICATION
ANCA +ve vasculitis/multisystem involvement
life threatening conditions
Steroid non responsive CSS and PAN
DOSE
2mg/kg/d preferred t/t
15 mg/kg thrice infusion every 2 weeks and then 3 weeks
SIDE EFFECTS include-BM suppression, cystitis,
infertility, GI intolerance, pulmonary fibrosis
51. METHOTREXATE
Indication
Limited WG non life threatening
Cyclophosphamide toxicity
Maintaining remission
Start at 0.3mg/kg/week increase by 2.5mg/wk upto max
of 25mg/wk to maintain remission level and then
decrease 2 yr post remission by 2.5mg/month and
discontinue
s/e hepatotoxicity, BM suppression, teratogenecity
AZATHIOPRINE AND MYCOPHENOLATE
Alternative to MTX and to maintain remission
dosage is 2mg/kg for azathioprine and 1gm bd for
mycophenolate
52. KAWASAKI DISEASE
High dose of 10mg/kg/d x14 days f/b 3-5
mg/kg/d for several weeks
Reduces coronary complications
GIANT CELL ARTERITIS
Reduces incidence of cerebral ischemic
complications
53. INDICATIONS
Kawasaki’s disease – 2g/kg single dose infusion
f/b high dose aspirin
Prevents aneurysmal formation
TAKAYASU ARTERITIS
Surgical treatment or angioplasty for stenosis
Reduces risk of stroke
Corrects HTN d/t RAS
54. HEPATITIS C RELATED CRYOGLOBULINEMIA
IFN- alpha preferred drug
3 million IU thrice weekly x 12 – 18 months
60 – 80% improvement
HEPATITIS B RELATED PAN
IFN a + vidarabine + lamivudine in combination
with plasma exchange
55. AGENT PRINCIPLE MECHANISM EVIDENCES SIDE EFFECTS
INFLIXIMAB
ADALIMUMAB
INTERFERENC
E WITH
GRANULOMA
FORMATION
TNF
BLOCKADE
EXPERIMENTAL
AND CLINICAL
EVIDENCES IN
AAV
ABDOMINAL
PAIN
CHEST PAIN
CHILLS/COUGH
RITUXIMAB DEPLETION
OF B-CELLS
ANTI CD-
20/22
EXPERIMENTAL
EVIDENCES IN
AAV
HEADACHE
FEVER
CHILLS
ERYTHROPOIE
TIN
PROMOTE
EPITHELIAL
PROGENITOR
CELL
FUNCTION
AND REPAIR
ENHANCE
VASCULAR
REPAIR
EXPERIMENTAL
AND CLINICAL
EVIDENCE
HTN
IRON
DEFICIENCY
FLU LIKE
ILLNESS
56. Upper and lower respiratory with renal involvement –
WEGENER’S GRANULOMATOSIS
Young female with arm/leg fatigue with bruits
TAKAYASU ARTERITIS
Old female with headache, jaw ache GIANT CELL
ARTERITIS
Child with purpura, abdominal pain, hematuria
HENOCH SCHOLEIN PURPURA
Child with fever and inflammatory lesions over eyes,
skin, KAWASAKIS DISEASE
Prior history of asthma/allergic rhinitis CHURGH
STRAUSS SYNDROME
Hepatitis B – PAN
Hepatitis C - CRYOGLOBULINEMIAS