lecture samy- 2-4-16

VASCULITIS

DR. SHANMUGASAMY.KASST PROFESSOR

Content :• Introduction • Classification of vasculitis• Pathogenesis • Large vessel vasculitis.• Medium sized vasculitis.• Small vessel vasculitis.

Introduction:• It is defined as inflammation of vessel walls.

• Most commonly affects small vessels like arterioles, capillaries and venules.

• FACTORS:- Vessel size, - Role of immune complexes, - Presence of specific autoantibodies, - Granuloma formation and - Organ specificity.

Blood vessels

CLASSIFICATION LARGE SIZED VESSELS– Temporal arteritis– Takayasu’s arteritis

MEDIUM SIZED VESSELS– Polyarteritis nodosa– Kawasaki’s disease

SMALL SIZED VESSELS– Wegener’s granulematosis– Churg-Strauss syndrome– Microscopic polyangiitis

Pathogenesis:CAUSES

INFECTIOUS IMMUNOLOGICAL - Immune complex

deposition - antineutrophil cytoplasmic

ab - anti–endothelial cell ab

1. Giant-Cell (Temporal) Arteritis

• Most common type of vasculitis• Patients >50, F:M = 2:1. • Chronic, granulomatous

inflammation of large to small arteries, especially in head particularly the branches of the carotid artery (temporal a. and branches of the ophthalmic a.)

• Involvment is segmental, acute and chronic.

Clinical Features

Symptoms : fever, facial pain or headache, often most intense

along the course of the superficial temporal artery, Thickened and painful temporal artery Jaw pain Visual problems and acute vision loss

The diagnosis depends on biopsy and histologic confirmation.

Treatment: corticosteroids

Giant-Cell (Temporal) Arteritis: morphology

Granulomatous inflammation of the blood vessel wall

Giant cells Disruption and fragmentation

of internal elastic lamina Proliferation of the intima with

associated occlusion of the lumen.

The healed stage reveals collagenous thickening of the vessel wall and the artery is transformed into a fibrous cord

Takayasu arteritis• Granulomatous vasculitis of medium and

larger arteries characterized principally by ocular disturbances and marked weakening of the pulses in the upper extremities -Pulseless disease .

• Takayasu arteritis manifests with transmural fibrous thickening of the aorta—particularly the aortic arch and great vessels—and severe luminal narrowing of the major branch vessels.

• Histological changes range from adventitial mononuclear infiltrates with perivascular cuffing of the vasa vasorum, to intense mononuclear inflammation in the media, to granulomatous inflammation, replete with giant cells and patchy medial necrosis.

Takayasu arteritis

Takayasu arteritis

Polyarteritis Nodosa• Disease of young adults.

• there is segmental necrotizing inflammation of arteries of medium to small size, in any organ (esp kidney) except the lung.

• Most frequently kidneys, heart, liver, and gastrointestinal tract.

• Polyarteritis nodosa has been associated with hepatitis B or hepatitis C

Polyarteritis Nodosa Clinical manifestations result from ischemia and

infarction of affected tissues and organs.

Weakening of the arterial wall due to the inflammatory process may cause aneurysmal dilation or localized rupture.

Fever, weight loss, abdominal pain and melena (bloody stool), muscular pain and neuritis.

Renal arterial involvement is often prominent and is a major cause of death.

Polyarteritis Nodosa

Ischemic ulcers

Particularly characteristic of PAN is that all the different stages of activity ( i.e. active and chronic stages) may coexist in same artery or in different vessels at the same time.

Fatal if untreated, but steroids and cyclophosphamide are curative.

Polyarteritis nodosa with segmental inflammation and fibrinoid necrosis and occlusion of the lumen of this artery. Note that part of the vessel wall at the left side is uninvolved.

Kawasaki disease• It is an acute febrile, usually self-limited illness of

infancy.

• Usually affects large to medium-sized, and even small, vessels.

• It is the leading cause of acquired heart disease in children.

• Coronary artery involvement- coronary arteritis can cause aneurysms that rupture or thrombosis.

Kawasaki disease- Morphology

• It exhibits pronounced inflammation affecting the entire thickness of the vessel wall.

• Fibrinoid necrosis is usually less prominent.

• Also leads to aneurysm formation with thrombosis .

• Obstructive intimal thickening.

• Kawasaki disease is also known as mucocutaneous lymph node syndrome.

• It presents with conjunctival and oral erythema and erosion, edema of the hands and feet, erythema of the palms and soles, a desquamative rash, and cervical lymph node enlargement.

• Approximately 20% of untreated patients develop cardiovascular sequelae- myocardial infarction, and sudden death.

Wegener granulomatosis is a necrotizing vasculitis characterized by the triad of

1) necrotizing granulomas of the upper and lower respiratory tract

2) necrotizing or granulomatous vasculitis of small to medium-sized vessels

3) renal disease in the form of necrotizing, crescentic, glomerulonephritis.

Wegener Granulomatosis

Males are affected more often than females, at an average age of about 40 years

C-ANCAs(antineutrophilic cytoplasmic antibodies) is positive in serum of more than 95% of patients.

Persistent pneumonitis , chronic sinusitis , mucosal ulcerations of the nasopharynx , and evidence of renal disease.

Untreated: fatal - may lead to death within 2 years if not treated.

Wegener granulomatosis: palatal ulceration

Wegener granulomatosis: palatal destruction

Wegener’s Granulomatosis

Orbital and nasal granuloma Pulmonary nodesAnd cavitation

WG

WG

WG

Churg-Strauss syndrome

• Eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels

• Associated with asthma and blood eosinophilia

• Associated with p-ANCAs.

Microscopic polyangitis

• Necrotizing small-vessel vasculitis with few or no immune deposits.

• necrotizing arteritis of small and medium-sized arteries can occur.

• Necrotizing glomerulonephritis and pulmonary capillaritis are common.

• Associated with MPO-ANCAs

Microscopic polyangitis

THROMBOANGIITIS OBLITERANS (BUERGER DISEASE)

• It leads to vascular insufficiency.

• it is characterized by segmental, thrombosing, acute and chronic inflammation of medium-sized and small arteries.

• Tibial and radial arteries, with occasional secondary extension into the veins and nerves of the extremities.

• Affects heavy cigarette smokers, usually before the age of 35.

• Cigarette smoking - Direct endothelial cell toxicity by some component of tobacco, or an idiosyncratic immune response to the same agents.

• Microscopically, there is acute and chronic inflammation, accompanied by luminal thrombosis.

• Typically, the thrombus contains small microabscesses composed of neutrophils surrounded by granulomatous inflammation.

• The inflammatory process extends into contiguous veins and nerves (rare with other forms ofvasculitis), and in time all three structures become encased in fibrous tissue.

TAO

TAKE HOME MESSAGE:

1. LARGE VESSEL VASCULITIS:s.no Disease Description

1. Giant-cell (temporal) arteritis Granulomatous inflammation; frequently involves the temporal artery. Usually occurs in patients older than age 50.

2. Takayasu arteritis Granulomatous inflammation usually occurring in patients younger than age 50

TAKE HOME MESSAGE

• 2. MEDIUM VESSEL VASCULITIS:

s.no Disease Description

1. Polyarteritis nodosa Necrotizing inflammation typically involving renal arteries but sparing pulmonary vessels

2. Kawasaki disease Arteritis with mucocutaneous lymph node syndrome; usually occurs in children. Coronary arteries can be involved with aneurysm formation and/or thrombosis.

TAKE HOME MESSAGE• 3. SMALL VESSEL VASCULITIS:

s.no Disease Description

1. Wegener granulomatosis Granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels, including glomerular vessels. Associated with PR3-ANCAs.

2. Churg-Strauss syndrome Eosinophil-rich granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small vessels. Associated with asthma and blood eosinophilia. Associated with MPO-ANCAs.

3. Microscopic polyangiitis Necrotizing small-vessel vasculitis.Necrotizing glomerulonephritis and pulmonary capillaritis are common.