Vasculitis Vasculitis Dr. Gehan Mohamed Dr. Abdelaty Shawky

* Definition: Inflammation of the blood vessels Clinically often include constitutional signs and symptoms such as fever, myalgia, arthralgia, and malaise, or local manifestations of tissue ischemia.

* Causes of vasculitis: 1. infection: pathogens either cause direct invasion of vascular walls or indirectly induce a noninfectious, systemic immune-mediated vasculitis, for example, by generating immune complexes or triggering cross-reactivity. 2. Physical and chemical injury: such as irradiation, mechanical trauma, and toxins can also cause vascular damage.

3. immune-mediated vasculitis: the vascular wall is damaged by different immune mechanisms; a.Immune complex deposition: a.Immune complex deposition: as in hypersensitivity to drugs, hepatitis B virus infection b.Anti-neutrophil cytoplasmic antibodies (ANCAs): b.Anti-neutrophil cytoplasmic antibodies (ANCAs): ANCAs are a heterogeneous group of autoantibodies directed against enzymes mainly found within the primary granules in neutrophils, in the lysosomes of monocytes, and in endothelial cells.

- The description of these autoantibodies is based on the immunofluorescent patterns of staining. - Two main patterns are recognized: one shows cytoplasmic localization of the staining (c-ANCA), and the most common target antigen is proteinase-3 (PR3), a neutrophil granule constituent. The second shows perinuclear staining (p-ANCA) and is usually specific for myeloperoxidase (MPO). - The disorders characterized by circulating ANCAs are called the ANCA-associated vasculitis.

c. Anti-endothelial cell antibodies: Antibodies to ECs, perhaps induced by defects in immune regulation, may predispose to certain vasculitis, such as those associated with SLE and Kawasaki disease.

* Classification of vasculitis: The systemic vasculitis are classified on the basis of : - the size and anatomic site of the involved blood vessels - histologic characteristics of the lesion, and - clinical manifestations. There is considerable clinical and pathologic overlap among these disorders

1. GIANT CELL (TEMPORAL) ARTERITIS -Is the most common form of systemic vasculitis in adults. -Affects old ages above the age of 50 years. - Is granulomatous inflammation of large sized arteries. - It affects principally the head arteries especially the temporal arteries, but also the vertebral and ophthalmic arteries and the aorta. Ophthalmic arterial involvement may lead to permanent blindness.

* Morphology: Characteristically, segments of affected arteries develop nodular thickenings with reduction of the lumen and may become thrombosed. Microscopically: granulomatous inflammation of the inner half of the media showing mononuclear infiltrate, multinucleate giant cells and fragmentation of the internal elastic lamina. The healed stage reveals collagenous thickening of the vessel wall with organization of the luminal thrombus. Sometimes transforms the artery into a fibrous cord.

* Pathogenesis: immunologic reaction against elastin. * Clinical Features: -Constitutional manifestations: fever, fatigue, weight loss. -Facial pain or headache, often most intense along the course of the superficial temporal artery, which may be painful to palpation. -Ocular symptoms (associated with involvement of the ophthalmic artery).

2. TAKAYASU ARTERITIS The illness is seen predominantly in females younger than age 40. This is a granulomatous vasculitis of large sized arteries especially aorta and ocular arteries. Clinically characterized principally ocular disturbances and marked weakening of the pulses in the upper extremities (pulseless disease).

* Morphology: Grossly: The affected vessel shows irregular thickening with intimal wrinkling. Microscopically: adventitial mononuclear infiltrate with perivascular cuffing of the vasa vasorum and granulomatous inflammation, with giant cells. Later, there is collagenous fibrosis involving all layers of the vessel wall.

3. POLYARTERITIS NODOSA (PAN) PAN is a systemic vasculitis of small or medium- sized muscular arteries (but not arterioles, capillaries, or venules), e.g. renal artery. Clinical manifestations result from ischemia and infarction of affected tissues and organs. Affects young adults. The course may be acute, subacute, or chronic.

The disease is fatal in most cases, either during an acute fulminant attack or following a protracted course, but therapy with corticosteroids and cyclophosphamide results in remissions or cures in 90% of cases.

* Morphology: Segmental transmural necrotizing inflammation with neutrophils,eosinophils and fibrinoid necrosis. The lumen may become thrombosed. Later, the acute inflammatory infiltrate disappears and is replaced by fibrous thickening of the vessel wall that may extend into the adventitia. Firm nodularity sometimes marks the lesions.

* Complications of PAN: 1. Thrombosis with subsequent ischaemic complications. 2. Aneurysmal dilatation. 3. Rupture during acute attacks with fatal hemorrhage.

4. KAWASAKI DISEASE (MUCOCUTANEOUS LYMPH NODE SYNDROME) -It is inflammation of the coronary arteries, usually in young children and infants (80% of cases are <4 years old). -Epidemic in Japan. - It is associated with the mucocutaneous lymph node syndrome, an acute but usually self-limited illness manifested by fever, conjunctival and oral erythema and erosion, edema of the hands and feet, erythema of the palms and soles, a skin rash often with desquamation, and enlargement of cervical lymph nodes.

* Morphology: Fibrinoid necrosis and pronounced inflammation affecting the entire thickness of the vessel wall. * Fate: Most of cases subsides spontaneously or in response to treatment. Some cases may be complicated by aneurysm formation, thrombosis, and/or myocardial infarction. Healed lesions may cause obstructive intimal thickening

* Pathogenesis: Immune reaction characterized autoantibodies to endothelial cells and smooth muscle cells, leading to acute vasculitis. Viral infection may trigger the disease in genetically susceptible patients.

5. MICROSCOPIC POLYANGIITIS - It is necrotizing vasculitis affects arterioles, capillaries. - In contrast to PAN, the affected vessels are smaller, necrotizing glomerulonephritis (90% of patients) pulmonary capillaritis are particularly common.

* Clinical features: Hemoptysis, arthralgia, abdominal pain, hematuria, proteinuria, hemorrhage, and muscle pain or weakness. * Pathogenesis: - Immunologic reaction to an antigen such as drugs (e.g., penicillin), microorganisms (e.g., streptococci), heterologous proteins, and tumor antigens. -In 70% of patients, p-ANCAs are present.

6.WEGENER GRANULOMATOSIS It is a necrotizing granuloma affecting triad of: 1. Respiratory tract. 2. Necrotizing granulomatous vasculitis affecting small to medium-sized vessels, mostly of the lungs and upper airways. (3) Kidney: in the form of glomerulonephritis.

8. THROMBOANGIITIS OBLITERANS (BUERGER DISEASE) Is characterized by segmental inflammation and, thrombosis of medium-sized and small arteries, principally the tibial and radial arteries Sometimes secondarily extending to veins and nerves of the extremities. Affects heavy cigarette-smoking men and women usually before age 35 in most cases.

Direct endothelial cell toxicity by some tobacco products or hypersensitivity to them. Stopping smoking in the early stages of the disease often prevents further attacks.

8. VASCULITIS ASSOCIATED WITH OTHER DISORDERS Such as rheumatoid arthritis, SLE, malignancy.

Thanks References: Robbins and Cotran’s: Pathologic Basis of Disease. Seventh edition.