VASCULITIS

Vasculitis is a general term for vessel wall inflammation.

  • The two most common pathogenic mechanisms of vasculitis are immune-mediated inflammation and direct vascular invasion by infectious pathogens.
  • Infections also can indirectly precipitate immune-mediated vasculitis
  • classification is made according to vessel diameter, role of immune complexes, presence of specific autoantibodies, granuloma formation, organ specificity, and even population demographics.

Non Infectious Vasculitis:

The mechanisms underlying non infectious vasculitis are:

  • Immune complex deposition
  • Anti neutrophil cytoplasmic antibodies
  • Anti EC antibodies
  • Autoreactive T cells
Immune Complex Associated Vasculitis:
  • This form of vasculitis is seen in immunologic disorders that are associated with autoantibody production like SLE.
  • The problem with this type of vasculitis is a diagnosis.
  • Very rarely the specific antigen responsible for immune complex formation known, because the immune complexes have been degraded by the time of biopsy.

Immune complex deposition is also implicated in the following vasculitides:

  • Drug hypersensitivity vasculitis.
  • Vasculitis secondary to infections.
Anti Neutrophil cytoplasmic Antibodies:

Many patients with vasculitis have circulating antibodies that react with neutrophil cytoplasmic antigens, so-called anti neutrophil cytoplasmic antibodies (ANCAs).

Of them the most important antibodies are:

  • Anti-proteinase-3 . PR3 is a neutrophil azurophilic granule constituent that shares homology with numerous microbial peptides which explains the generation of PR3-ANCAs.
  • Anti-myeloperoxidase. MPO-ANCAs are induced by several therapeutic agents, particularly propylthiouracil  which is used to treat hyperthyroidism.

Gaint Cell Arteritis:

  • Giant cell  arteritis is a chronic inflammatory disorder, typically with granulomatous inflammation, that principally affects large- to small-sized arteries in the head.
  • Also called Temporal arteritis, because the diagnose is mainly done from the biopsy of these arteries.
  • Vertebral and ophthalmic arteries, as well as the aorta are other common sites of involvement.
  • Ophthalmic artery vasculitis can lead to sudden and permanent blindness.
Pathogenesis:
  • Giant cell arteritis likely occurs as a result of a T-cell– mediated immune response to an as yet uncharacterized vessel wall antigen.
  • Pro inflammatory cytokines like TNF and anti EC antibodies also contribute.
  • The characteristic granulomatous inflammation, an association with certain MHC class II haplotypes, and the excellent therapeutic response to steroids, all strongly support an immune etiology.
Clinical Features:
  • Temporal arteritis is rare before 50 years of age. Signs and symptoms may be vague ex : fever, fatigue, weight loss.
  • Involvement of opthalmic artery may cause diplopia or permanent blindness.
Morphology:
  • The pathologic changes are patchy along the length of the vessel.
  • The vessels involved show intimal thickening narrowing the vessel lumen.
  • Most of the lesions are Granulomatous Inflammation in the inner media.
  • Fragmentation of the internal elastic lamina is seen.

Takayasu Arteritis: 

  • Takayasu arteritis is a granulomatous vasculitis of medium- and large-sized arteries.
  • It characterized principally by ocular disturbances and marked weakening of the pulses in the upper extremities
  • Hence it is called as pulseless disease.
  • The main features of this disorder is with transmural scarring and thickening of the aorta particularly the aortic arch and great vessels with severe luminal narrowing of the major branch vessels.
  • It shares many features with Gaint cell arteritis. Hence the differentiation is made mostly on age, if above 50 years Gaint cell arteritis , below 50 years is Takayasu arteritis.
Morphology:
  • Occasionally, aortic root involvement causes dilation and aortic valve insufficiency.
  • Histologic picture encompasses a spectrum ranging from adventitial mononuclear infiltrates and perivascular cuffing of the vasa vasorum, to intense transmural mononuclear inflammation,to granulomatous inflammation, replete with giant cells and patchy medial necrosis.
  • The inflammation is associated with irregular thickening of the vessel wall, intimal hyperplasia, and adventitial fibrosis.

Polyarteritis Nodosa:

  • Polyarteritis nodosa (PAN) is a systemic vasculitis of small- or medium-sized muscular arteries.
  • It typically involves the renal and visceral vessels and spares the pulmonary circulation.
  • It is commanly associated with Hepatitis B antigen.
Morphology:
  • Classic PAN is a segmental transmural necrotizing inflammation of small to medium sized arteries.
  • Kidney,heart,liver,and gastrointestinal tract vessels are affected in descending order of frequency.
  • Lesions of varying stages are present. Early lesion consists of transmural inflammation with fibrinoid necrosis

Kawasaki Disease:

  •  Classically affects Asian  below 4 years old
  •  Presents with nonspecific signs including fever, conjunctivitis, erythematous rash of palms and soles, and enlarged cervical lymph nodes
  • Coronary artery involvement is common and leads to risk for (1) thrombosis with myocardial infarction and (2) aneurysm with rupture.
  • Treatment is aspirin and IVIG; disease is self-limited.

 Buerger Disease:

  • Necrotizing vasculitis involving digits
  • Presents with ulceration, gangrene, and autoamputation of fingers and toes; Raynaud phenomenon is often present.
  • Highly associated with heavy smoking; treatment is smoking cessation.

Wegener Granulomatosis

  • 1. Necrotizing granulomatous vasculitis involving nasopharynx, lungs, and kidneys
  • 2. Classic presentation is a middle-aged male with sinusitis or nasopharyngeal ulceration, hemoptysis with bilateral nodular lung infiltrates, and hematuria due to rapidly progressive glomerulonephritis.
  • 3. Serum c-ANCA levels correlate with disease activity.
  • 4. Biopsy reveals large necrotizing granulomas with adjacent necrotizing vasculitis
  • 5. Treatment is cyclophosphamide and steroids; relapses are common.

Microscopic Polyangiitis

  • 1. Necrotizing vasculitis involving multiple organs, especially lung and kidney
  • 2. Presentation is similar to Wegener granulomatosis, but nasopharyngeal involvement and granulomas are absent.
  • 3. Serum p-ANCA levels correlate with disease activity.
  • 4. Treatment is corticosteroids and cyclophosphamide; relapses are common.

Churg-Strauss Syndrome

  • 1. Necrotizing granulomatous inflammation with eosinophils involving multiple organs, especially lungs and heart
  • 2. Asthma and peripheral eosinophilia are often present.
  • 3. Serum p-ANCA levels correlate with disease activity.

Infectious vasculitis:

  • Localized arteritis may be caused by the direct invasion of arteries by infectious agents, usually bacteria or fungi, and in particular Aspergillus and Mucor spp.
  • Vascular infections may weaken arterial walls and culminate in mycotic aneurysms, or may induce thrombosis and infarction.
  • Thus, inflammation of vessels in bacterial meningitis can cause thrombosis and infarction, leading ultimately to extension of a subarachnoid infection into the brain parenchyma.

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