vasculitis

1. SPEAKER :DR CHANDAN DEEP
MODERATOR :DR GURPAL SACHDEVA

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

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

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

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

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

21.  DIAGNOSIS CRITERIA
 PRESENCE OF 5/6 CONDITIONS
 Fever lasting 5 days
+
 Bilateral bulbar conjunctivitis(non purulent)
 Oropharyngeal mucosal changes(injected
pharynx/dry fissured lips)
 Rash(truncal non vesicular)
 Peripheral extremities (periungal desquamation)
 Cervical lymphadenopathy > 1.5 cm unilateral

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

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

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

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

38.  BACTERIAL ENDOCARDITIS
 DISSEMINATED GONOCOCCAL INFECTION
 ROCKY MOUNTAIN SPOTTED FEVER
 LYME’S DISEASE
 ANTIPHOSPHOLIPID ANTIBODY SYNDROME
 THROMBOTIC THROMBOCYTOPENIC PURPURA
 SARCOIDOSIS
 NEOPLASMS LIKE ATRIAL MYXOMA, LYMPHOMAS
 THORACIC OUTLET SYNDROME
 SEPSIS/DIC
 SARCOIDOSIS
 DRUGS – COCAINE, AMPHETAMINES, ERGOTS,
ARSENIC

39.  CONNECTIVE TISSUE DISORDERS like SLE,
Sjogrens syndrome, RA, scleroderma
 MALIGNANCY like lymphomas, leukemia
 BROCHIAL ASTHMA
 HIV
 INTAKE OF DRUGS
 HYDRALAZINE
 PROPYLTHIOURACIL
 ALLOPURINOL
 GOLD
 SULPHONAMIDES
 PENICILLIN

40.  GENERAL EXAMINATION
 PALLOR
 LYMPH NODES
 PULSE AND BLOOD PRESSURE
 SKIN
 EYES NOSE AND ORAL CAVITY

41.  CNS
 TIA/STROKE
 VISUAL LOSS
 MONONEURITIS MULTIPLEX
 CVS
 CHF
 ANGINA/MI
 RESPIRATORY
 CAVITORY LESIONS
 FLEETING INFILTRATES

42.  RENAL
 HEMATURIA
 HTN
 OLIGURIA
 GIT
 ABDOMINAL TENDERNESS
 MALEANA

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

46.  ARTERIOGRAPHY
 Aortic – takayasu
 Cerebral – isolated CNS vasculitis
 Renal – PAN
 Coronary – kawasaki
 CHEST X- RAY –
 Infiltrates – small vessel vasculitis
 Cavities – wegeners granulomatosis

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

48. DOMINANT
VESSEL
CORTICOSTEROIDS
ALONE
CYCLOPHOSPHAMIDE +
CORTICOSTEROIDS
OTHER
TREATMENT
LARGE
ARTERIES
+++ - +
MEDIUM
ARTERIES
+ ++ ++
SMALL AND
MEDIUM
ARTERIES
+ +++ +
SMALL
VESSELS
+ +/- ++

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