VASCULITIS

DR ASHNA MALHOTRA
• Vasculitis literally means inflammation of a
blood vessel wall.
• It is defined as a primary, focal,
inflammatory process involving blood
vessels after excluding an embolus, thrombus
or an extravascular source.
 CLASSIFICATION

• In 1994, the Chapel Hill Consensus Conference addressed the

nomenclature problems relating to primary systemic
vasculitides, aiming to create a standardized nomenclature.

• This system divided the vasculitides into small, medium and

large vessel types, but specifically did not aim to determine
clinical criteria for classification or diagnosis of individual
patients.
 CHAPEL HILL CONSENSUS
CONFERENCE CLASSIFICATION

• LARGE VESSEL VASCULITIS

• Giant cell arteritis
• Takayasu’s arteritis

• MEDIUM-SIZED VESSEL VASCULITIS

• Classic polyarteritis nodosa
• Kawasaki disease
• SMALL VESSEL VASCULITIS
• Wegener’s granulomatosis
• Churg–Strauss syndrome
• Microscopic polyangiitis (polyarteritis)
• Henoch–Schönlein purpura
• Essential cryoglobulinaemia
• Cutaneous leukocytoclastic vasculitis
 PROPOSED WORKING CLASSIFICATION
OF VASCULITIS

Small vessel vasculitis

• Cutaneous small vessel vasculitis—not further classified
• Henoch–Schönlein purpura
• Essential mixed cryoglobulinaemia
• Waldenström’s hypergammaglobulinaemic purpura
• Associated with collagen vascular disease
• Urticarial vasculitis
• Erythema elevatum diutinum
• Eosinophilic vasculitis
• Rheumatoid nodules
• Reactive leprosy
• Septic vasculitis
Larger vessel vasculitis
• Polyarteritis nodosa
• Microscopic polyarteritis
• Cutaneous form
• Systemic form
• Granulomatous vasculitis
• Wegener’s granulomatosis
• Allergic granulomatosis of Churg and Strauss
• Lymphomatoid granulomatosis
• Giant cell arteritis
• Temporal arteritis
• Takayasu’s arteritis

Larger vessel vasculitis with collagen vascular disease

Nodular vasculitis
 CONDITIONS WHERE VASCULITIS
SHOULD BE SUSPECTED

• Fever of unknown origin

• Multisystem disease
• Active glomerulonephritis
• Ischemic symptoms in young patients
• Palpable purpura
• Mononeuritis multiplex
 PATHOGENESIS

• PATHOGENETIC FACTORS:
1. Immune complex deposition
2. Complement activation
3. Anti- neutrophil cytoplasmic antibodies
4. Vascular endothelial cell
5. Cell- mediated immunity
• In immune complex-mediated vasculitis, circulating antigens (e.g. infectious agents,
medications, neoplasms) induce antibody formation.
• Binding of antibodies to circulating antigens creates immune complexes.
• Immune complex deposition within postcapillary venules activates complement and
subsequently leads to an increase in adhesion molecule expression on the
endothelium.
• Complement split products (C3a and C5a) induce mast cell degranulation and
neutrophil chemotaxis.
• Mast cell degranulation leads to increased vascular dilation and permeability,
enhancing immune complex deposition and leukocyte tethering to endothelium.
• Increased adhesion between inflammatory cells (especially neutrophils) and the
endothelium is mediated by elevated expression of selectins (E-selectin, P-selectin)
and members of the immunoglobulin superfamily (ICAM-1, VCAM-1, PECAM-1)
on endothelial cells in concert with the upregulation of their corresponding ligands
and receptors/adhesion molecules on leukocytes (e.g. P-selectin glycoprotein ligand-
1, LFA-1, Mac-1)
• Neutrophils release proteolytic enzymes (such as collagenases and elastases) and
free oxygen radicals that damage the vessel wall.
• In addition, formation of the membrane attack complex (C5–C9) on the endothelium
leads to the activation of the clotting cascade and the release of cytokines and
growth factors with ensuing thrombosis, inflammation and angiogenesis.
• In ANCA-mediated vasculitis, intracellular proteins from neutrophils (e.g.
proteinase 3 [PR3], myeloperoxidase [MPO]) become expressed on the
cell surface.
• After formation of ANCA that recognize these antigens, binding of the
autoantibodies to neutrophils leads to increased neutrophil adhesion to
vessel walls and subsequent cellular activation.
• Neutrophils then release reactive oxygen species and other toxic
mediators that result in vessel wall damage.
• Because the vessel damage in ANCA-positive vasculitides is directly
mediated by neutrophils rather than by immune complexes, they are
referred to as “pauci-immune” vasculitides.
                                                         
LARGE ‐ VESSEL VASCULITIS
 GIANT CELL ARTERITIS

Giant cell arteritis (GCA) is an arteritis, often granulomatous,

usually affecting the aorta and/or its major branches, with a
predilection for the branches of the carotid and vertebral arteries.
Since superficial temporal artery is also involved, and may lead to
serious complications like blindness, it is also known as Temporal
arteritis
• Epidemiology
• This affects people over the age of 50.
• The disease is 2–3 times more common in women than men
 CLINICAL FEATURES

• Fever and weight loss may occur.

• Headache may be localized to the area of the affected artery, that is
temporal with temporal arteritis and occipital with vertebrobasilar
arteritis. The headache may start abruptly.
• Facial pain may occur on chewing due to claudication of the jaw
muscles.
• Sudden, permanent visual loss related to ocular or orbital artery
involvement may occur.
• Rare complications: Scalp and tongue necrosis
• Temporal artery- thickened, tender, pulseless
 DIAGNOSIS

• Acute phase reactants are raised, anemia and

thrombocytosis is common.
• The gold standard for diagnosis is temporal artery biopsy.
• Ultrasound imaging shows a hypoechogenic wall
thickening with duplex sonography called “halo sign”,
indicating vessel wall inflammation.
• PET is useful to assess involvement of intrathoracic
vessels
 MANAGEMENT

• First line
• Corticosteroids, for example prednisolone 1 mg/kg/day, are used for
GCA. The dose can usually be reduced slowly in small steps every
month, providing that the CRP/ESR levels remain controlled.
• Second line
• There is some evidence of the steroid‐sparing ability of
methotrexate, which can be used in doses of 15–20 mg/week and
may be useful in preventing ischemic complications
 TAKAYASU ARTERITIS

• Takayasu arteritis is a chronic inflammatory disease, often

granulomatous and predominantly affects the aorta and/or its major
branches.
• Also known as Pulseless disease, non specific aorto arteritis, middle
aortic syndrome.
• Epidemiology
• The disease is seen in younger people, typically below the age of 50.
• females > males.
 CLINICAL FEATURES

• Most common sign: Hypertension. Most often due to Renal artery

stenosis.
• Neurological manifestations such as headache, stroke, visual
disturbances due to narrowing of carotid and subclavian arteries.
• Eyes- Retinopathy, cataract, optic atrophy
• Cutaneous lesions are present in around one ‐third of patients.
• Common- Erythema nodosum
• Others include: erythema induratum and pyoderma gangrenosum, as
well as ulcerated subacute nodular lesions, papulonecrotic eruptions,
papular erythematous lesions of the hands and fingers, facial lupus ‐like
rashes and panniculitis.
 DIAGNOSIS

• Mild anemia, leukocytosis, elevated ESR

• Radiological findings consist of segmental, dystrophic
calcification.
• The extent of vessel involvement can be gauged by angiogram.
• The most significant finding of angiogram is skipped areas of
aortic involvement.
• CT, MRI
 DIAGNOSTIC CRITERIA

• American college of rheumatology, 1990.

• Sensitivity is low, although may be useful at the bedside.
• 3 out of 6 needed for diagnosis
1. Age of onset <40 years
2. Claudication at extremities
3. Decreased brachial artery pulse
4. Difference of >10 mm Hg systolic BP between limbs
5. Bruit over subclavian artery or aorta
6. Angiographic evidence of narrowing/ occlusion of entire aorta or branches.
 MANAGEMENT

• First line
• Prednisolone 1 mg/kg/day is the usual favoured first line
treatment. There is some evidence for the addition of
azathioprine as an adjunct to corticosteroid therapy.
• Second line
• Cyclophosphamide, infliximab and tocilizumab have been
reported to be of anecdotal value.
Treatment of hypertension and vessel complications.
• Treatment of choice is – Percutaneous Transluminal angioplasty (PTA)
• Arterial grafting may be done.
MEDIUM ‐ VESSEL VASCULITIS
 POLYARTERITIS NODOSA

• Definition and nomenclature

• Polyarteritis nodosa (PAN) is a rare necrotizing arteritis of medium
or small arteries without glomerulonephritis and without vasculitis in
the arterioles, capillaries or venules.
• Epidemiology
• The peak age is between 40 and 60 years of age.
• PAN can be the first manifestation of hepatitis B and occurs in most
cases within 6 months of infection.
 ETIOPATHOGENESIS

• Majority cases- Cause unknown

• Sometimes: Infections- mainly viral, particularly HBV
• Other viruses HCV, Parvovirus B19
• Rare association with hairy cell leukemia
• Other antigens demonstrated in vasculitic skin lesions- Streptococcus,
Staphylococcus, Mycobacteria.
 CLINICAL FEATURES

• Although some patients with cutaneous arteritis may report

constitutional symptoms, along with mild involvement of the
muscles and nerves, cutaneous manifestations are the most
striking feature of the disease.
• Dermal or subcutaneous nodules are most commonly located
on the distal lower extremities near the malleoli and may
extend proximally to the thighs, buttock, arms or hands.
• Patients may report tenderness associated with the nodules, which
may ulcerate or more commonly demonstrate necrotizing livedo
reticularis, also referred to as retiform purpura
• Gangrene of the digits can ultimately occur, most commonly in
children with cutaneous arteritis, but this finding should trigger
an aggressive search to exclude systemic features of PAN.
 PATHOLOGY

• Early in the disease course, there is a predominantly neutrophilic

inflammatory infiltrate in the walls of medium‐sized arteries and
arterioles of septae in the upper portions of the subcutaneous fat.
• The involved vessels classically demonstrate a target‐like
appearance resulting from an eosinophilic ring of fibrinoid necrosis.
• Later in the disease process, the infiltrate becomes less neutrophilic,
consisting predominantly of lymphocytes and histiocytes.
 TREATMENT

• Glucocorticoids are the treatment of choice.

• Prednisolone 1mg/kg/day maybe combined with
cyclophosphamide.
• Anti-viral therapy with vidarabin, interferon or
lamivudine is indicated if HBV serology is positive.
 CUTANEOUS POLYARTERITIS
NODOSA

• It is mostly confined to the skin with some extracutaneous

symptoms like fever, myalgia, arthralgia, malaise and neuropathy.
• Etiology
• It is thought to be caused by infectious agents like group A beta hemolytic
streptococcus.
• Most patients have an episode of upper RTI before onset of illness.
• A few patients have positive HCV serology.
• Correlation with inflammatory bowel disease
• Drugs like Minocycline
Disease is immune- complex mediated, DIF shows IgM and C3 deposits
within affected arterial walls. These ICs activate classical complement
pathway to cause CPAN
 CLINICAL FEATURES

• The presenting features of cPAN are livedo reticularis,

tender subcutaneous nodules or cutaneous ulcers.
• Others like purpura, necrosis and autoamputation may
occur.
• There is a definite predilection for lesions to occur on the
legs.
 • Most common clinical finding- small, tender nodules that are better felt than
seen.
• These may progress to ulceration
• “Star burst” pattern of livido reticularis may be seen around the ulcer
• Constitutional symptoms like fever, myalgia and arthropathy are seen.
• It runs a chronic and intermittent course with acute flares lasting between 2 and
8 weeks.

• Diagnosis and investigations

• Non specific changes like anemia, leukocytosis and raised ESR are present.
• Anti streptococcal O titre and throat swab for culture of streptococcus are
mandatory in children.
• pANCA for minocycline induced PAN
• Biopsy of nodule to confirm diagnosis.
 TREATMENT

• Mild cases are treated with NSAID’s and colchicine.

• More severe cases are treated with systemic drugs like
corticosteroids and immunosuppressives.
• IVIG
• Dapsone and pentoxyphyllin can be tried.
• Prophylactic penicillin
• Hyperbaric oxygen
 KAWASAKI DISEASE

• Mucocutaneous lymph node syndrome

• It is an acute, multisystem, self limited vasculitis
that occurs primarily in children and is a
leading cause of acquired heart diseases in
developing countries.
• Epidemiology
• The disease almost always occurs in children.
• There is a mild male predilection.
• Causative organisms
• The disease is thought to be triggered by as yet
unidentified infectious agents.
 CLINICAL FEATURES

• Patients present with at least 5 days of fever, irritability, vomiting, anorexia,

cough, diarrhoea, runny nose, weakness and abdominal and joint pain.
• The disease typically has an initial acute, febrile stage lasting up to 2 weeks, a
second phase lasting 4–6 weeks when the risk of death from coronary
aneurysms is greatest, followed by a convalescent phase lasting up to 3 months.
• The fever is typically spiking and unresponsive to paracetamol.
• Pronounced reddeng of palms and soles- early sign
• There is acral and perianal erythema and acral oedema- non pitting edema of
distal parts of extremities
• Bilateral conjuncitivitis with anterior uveitis, fissured lips and a strawberry
tongue
• Non suppurative cervical lymphadenopathy, typically a single large cervical
node.
 PATHOLOGY

• Panarteritis of coronary arteries

• Inflammatory cells- Lymphocytes and histiocytes, but no giant cells
• Disruption of elastic membranes, areas of necrosis, aneurysm formation
• Other vessels involved less frequently
• Differential diagnosis
• Scarlet fever, systemic‐onset juvenile idiopathic arthritis and
erythema multiforme.
• Diagnosis
• This is mostly clinical.
• Raised ESR and thrombocytosis are useful tests.
• ECG may be performed
 MANAGEMENT

• First line
• Intravenous immunoglobulin and aspirin should be given early.
• Aspirin 80-100 mg/kg/day is given initially until the fever has settled and is then
reduced to 3–5 mg/kg/day for 6–8 weeks.
• All children should receive IVIg, usually given as a single dose of 2 g/kg over 12
h.
• Second line
• For children who remain febrile 36 h after the first dose of IVIg, a further dose of
2 g/kg can be given.
• Patients who are unresponsive to IVIg can be treated with high‐dose
prednisolone 2 mg/kg/day, which should be tapered after normalization of the
CRP
• Infliximab- recent treatment approach
• Surgical intervention in case of coronary artery involvement.
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