Systemic vasculitis
Necrotizing vasculitis, also called systemic necrotizing vasculitus, is a category of vasculitis, comprising vasculitides that present with necrosis. Examples include giant cell arteritis, microscopic polyangiitis, and granulomatosis with polyangiitis. ICD-10 uses the variant "necrotizing vasculopathy". ICD-9, while classifying these conditions together, does not use a dedicated phrase, instead calling them "polyarteritis nodosa and allied conditions". When using the influential classification known as the "Chapel Hill Consensus Conference", the terms "systemic vasculitis" or "primary systemic vasculitides" are commonly used. Although the word "necrotizing" is omitted, the conditions described are largely the same. Classification. Large vessel vasculitis. Giant-cell arteritis  and Takayasu's arteritis have much in common, but usually affect patients of different ages, with Takayasu's arteritis affecting younger people, and giant-cell arteritis having a later age of onset. Aortitis can also be considered a large-vessel disease. "Takayasu arteritis". Primarily affects the aorta and its main branches. At least three out of six criteria yields sensitivity and specificity of 90.5 and 97.8%: "Giant cell (temporal) arteritis". Chronic vasculitis of both large and medium vessels, primarily affecting cranial branches of the arteries arising from the aortic arch. At least three out of five criteria yields sensitivity and  specificity of 95 and 91%: Medium vessel vasculitis. These conditions are sometimes considered together with the small vessel vasculitides. "Polyarteritis nodosa" (PAN). Systemic necrotizing vasculitis and aneurysm formation affecting both medium and small arteries. If only small vessels are affected, it is called microscopic polyangiitis, although it is more associated with granulomatosis with polyangiitis than to classic PAN. At least 3 out of 10 criteria yields sensitivity and specificity of 82 and 87%: "Kawasaki disease". Usually in children (age<4), it affects large, medium, and small vessels, prominently the coronary arteries. Associated with a mucocutaneous lymph node syndrome. Diagnosis requires fever  lasting five days or more with at least four out of five criteria: "Isolated cerebral vasculitis". Affects medium and small arteries over a diffuse CNS area, without symptomatic extracranial vessel involvement. Patients have CNS symptoms as well as cerebral vasculitis by angiography and leptomeningeal biopsy. Small vessel vasculitis. There are several vasculitides that affect small vessels. Pauci-immune. "Granulomatosis with polyangiitis". Systemic vasculitis of medium and small arteries, including venules and arterioles. Produces granulomatous inflammation of the respiratory tracts and necrotizing, pauci-immune glomerulonephritis. Most common cause of saddle nose deformity in USA (nose flattened due to destruction of nasal  septum by granulomatous inflammation). Almost all patients with granulomatosis with polyangiitis have c-antineutrophil cytoplasmic antibody, but not vice versa. Current treatment of choice is cyclophosphamide. At least two out of four criteria yields sensitivity and specificity of 88 and 92%. "Eosinophilic granulomatosis with polyangiitis" (formerly known as Churg–Strauss syndrome). Affects medium and small vessels with vascular and extravascular granulomatosis. Classically involves arteries of lungs and skin, but may be generalized. At least four criteria yields sensitivity and specificity of 85 and 99.7%. "Microscopic polyarteritis/polyangiitis". Affects capillaries, venules, or arterioles. Thought to be part of a group that  includes granulomatosis with polyangiitis since both are associated with antineutrophil cytoplasmic antibody and similar extrapulmonary manifestations. Patients do not usually have symptomatic or histologic respiratory involvement. Immune complex. "Hypersensitivity vasculitis (allergic vasculitis)". Usually due to a hypersensitivity reaction to a known drug. Drugs most commonly implicated are penicillin, sulphonamides and thiazide diuretics. Methamphetamine and other sympathomimetics can cause a cerebral vasculitis alongside polyarteritis nodosa like systemic features. With other drugs,there is presence of skin vasculitis with palpable petechiae or purpura. Biopsy of these lesions reveal inflammation of the small vessels, termed leukocytoclastic vasculitis, which is most prominent in postcapillary  venules. At least three out of five criteria yields sensitivity and specificity of 71 and 84%: "IgA vasculitis" (formerly known as Henoch–Schonlein purpura). Systemic vasculitis due to tissue deposition of IgA-containing immune complexes. Biopsy of lesions shows inflammation of small vessels. It is considered a form of hypersensitivity vasculitis but is distinguished by prominent deposits of IgA. This is the most common vasculitis in children. Presence of three or more criteria yielded sensitivity of 87% while less than two criteria yielded hypersensitivity vasculitis in 74%: "Essential cryoglobulinemic vasculitis". Most often due to hepatitis C infection, immune complexes of  cryoglobulins – proteins that consists of immunoglobulins and complement and precipitate in the cold while dissolving upon rewarming – are deposited in walls of capillaries, venules, or arterioles. Therefore, complement will be low with histology showing vessel inflammation with immune deposits. Other/ungrouped. "Vasculitis secondary to connective tissue disorders". Usually secondary to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, Behçet's disease, and other connective tissue disorders. "Vasculitis secondary to viral infection". Usually due to hepatitis B and C, human immunodeficiency virus, cytomegalovirus, Epstein–Barr virus, and parvovirus B19. Signs and symptoms. Patients usually present with systemic symptoms with single  or multiorgan dysfunction. Common (and nonspecific) complaints include fatigue, weakness, fever, joint pains, abdominal pain, hypertension, chronic kidney disease, and neurologic dysfunction. The following symptoms should raise a strong suspicion of a vasculitis: Diagnosis. A detailed history is important to elicit any recent medications, any risk of hepatitis infection, or any recent diagnosis with a connective tissue disorder such as systemic lupus erythematosus (SLE). A thorough physical exam is needed as usual. Treatment. Treatment is targeted to the underlying cause. However, most vasculitis in general are treated with steroids (e.g., methylprednisolone) because the underlying cause of the vasculitis is due  to hyperactive immunological damage. Immunosuppressants such as cyclophosphamide and azathioprine may also be given. A systematic review of antineutrophil cytoplasmic antibody-positive vasculitis identified best treatments depending on whether the goal is to induce remission or maintenance and depending on severity of the vasculitis.