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  • DISEASEOF THE MONTH

    ANCA Small-Vessel Vasculitis

    RONALD J. FALK* and J. CHARLES JENNETTEt

    *Department of Medicine and Department of Pathology and Laboratory Medicine, University of North

    Carolina at Chapel Hill, Chapel Hi!!, North Carolina.

    Small-vessel vasculitis (SVV) that is injurious to the kidney

    includes immune complex-mediated vasculitis, such as He-

    noch-Sch#{246}nlein purpura and cryogbobulinemic vasculitis, and

    necrotizing vasculitis associated with anti-neutrophil cytoplas-

    mic autoantibodies (ANCA), such as microscopic polyangiitis

    and Wegeners granubomatosis. The most frequent renal lesion

    caused by SVV is glomerubonephritis, whereas barge-vessel

    vasculitis (LVV) and medium-sized-vessel vasculitis (MVV)

    do not cause glomerubonephritis but may cause renal dysfunc-

    tion secondary to ischemia.

    In 1993, the Chapel Hill Consensus Conference for the

    Nomenclature of Systemic Vasculitis ( 1 ) agreed on the namesand definitions of many vasculitides that affect the kidneys

    (Table 1 ). These names and definitions are used in this review.

    LVV, such as giant-cell arteritis and Takayasu arteritis, rarely

    cause clinically significant renal disease (2). When a LVV does

    cause renal dysfunction, it is usually in the form of the reno-

    vascular hypertension secondary to disease in the main renal

    arteries or in the aorta at the ostia of the renal arteries. MVV,

    including pobyarteritis nodosa and Kawasaki disease, results in

    necrotizing inflammation of arteries without inflammation in

    vessels other than arteries, including no glomerulonephritis (2).

    MVV may cause aneurysmal dilation, thrombosis, and rupture

    of renal arteries, resulting in infarction and hemorrhage (1,2).

    Patients with pauci-immune SVV, such as microscopic poly-

    angiitis, Wegeners granubomatosis, and Churg-Strauss syn-

    drome, have a high frequency of ANCA (1,2). ANCA react

    with cytoplasmic constituents of neutrophils and monocytes

    (3,4). Approximately 90% of cytoplasmic-staining ANCA

    (C-ANCA) react with a serine proteinase called proteinase 3

    (PR3-ANCA). In patients with SVV, approximately 90% of

    perinuclear-staining ANCA (P-ANCA) react with myeboper-

    oxidase (MPO-ANCA). In ANCA-positive patients who do not

    have SVV or gbomerubonephritis, such as patients with ulcer-

    ative colitis, primary sclerosing choleangiitis, or Feltys syn-

    drome, many P-ANCA have specificity for antigens other than

    MPO, such as lactoferrin and elastase.

    PR3-ANCA are most common in patients with Wegeners

    granubomatosis, but are not specific for this disease. Our own

    data, as well as that of a recent European vascubitis study group

    (E. Christiaan Hagen, personal communication), indicate that

    Correspondence to Dr. Ronald J. Falk. UNC School of Medicine, Division of

    Nephrology and Hypertension, 349 MacNider Bldg./CB 7155, Chapel Hill, NC27599-7155.

    1046-6673/0802-03 14$03.00/0

    Journal of the American Society of NephrologyCopyright U 1997 by the American Society of Nephrology

    approximately 65% of patients with Wegeners granubomatosis

    have PR3-ANCA and approximately 20% have MPO-ANCA

    (Table 2). PR3-ANCA are also found in patients with micro-

    scopic polyangiitis and necrotizing gbomerulonephritis without

    evidence for systemic SVV, although MPO-ANCA are more

    common in these diseases. MPO-ANCA and PR3-ANCA oc-

    cur in patients with Churg-Strauss syndrome, but relative fre-

    quencies are poorly defined because of the small numbers of

    patients who have been studied. Thus, although there are

    different frequencies of PR3-ANCA and MPO-ANCA among

    different types of SVV, neither ANCA subtype provides a

    diagnostic test that allows for the diagnostic differentiation

    among different phenotypes of ANCA-SVV. However, in a

    patient with signs and symptoms of SVV, ANCA positivity

    does confirm the presence of some form of ANCA-associated

    SVV, which is often useful for directing management even if

    the specific type of ANCA-SVV has not yet been determined.

    Pathologic FeaturesThe characteristic acute vascular lesion of ANCA-SVV is

    focal fibrinoid necrosis of vessels with associated leukocyte

    infiltration, frequently with leukocytoclasia. In a given patient,

    this lesion may affect any or all of the following vessels:

    arteries, arterioles, venules, and capillaries, especially gbomer-

    ular capillaries and pulmonary alveolar capillaries (2,5). The

    major clinicopathologic categories of systemic ANCA-vascu-

    bitis are microscopic polyangiitis, Wegeners granubomatosis,

    and Churg-Strauss syndrome. Crescentic gbomerubonephritis is

    a frequent component of systemic ANCA-vasculitis, and also

    occurs as a renal-limited form of ANCA-vasculitis (ANCA-

    ON). Microscopic polyangiitis, Wegener s granulomatosis,

    and Churg-Strauss syndrome all share pathologically identical

    necrotizing inflammation in small vessels. Wegeners granu-

    bomatosis is distinguished by the presence of necrotizing gran-

    ubomatous inflammation, Churg-Strauss syndrome by the pres-

    ence of asthma and eosinophilia, and microscopic pobyangiitis

    by the absence of granulomatous inflammation and asthma

    (Table 1). Severe necrotizing gbomerulonephritis is a frequent

    component of the vascular inflammation in Wegeners granu-

    lomatosis and microscopic polyangiitis, but necrotizing gb-

    merulonephritis is less frequent and usually less severe in

    Churg-Strauss syndrome.

    In the kidneys of patients with any type of ANCA-SVV,

    gbomerular capillaries are affected most often, resulting in

    necrotizing glomerubonephritis, usually with crescent forma-

    tion (Figure 1 , A and B). Arterioles, arteries, and interstitial

    capillaries/venubes (especially medullary vasa recta) may also

    be involved (Figure 1 , C and D). Interlobular and arcuate

  • Large-vessel vasculitis

    giant-cell (temporal) arteritis

    Takayasu arteritis

    Medium-sized vessel vasculitis

    polyarteritis nodosa

    Kawasaki disease

    Small-vessel vasculitis

    Wegener 5 granulomatosis

    Churg-Strauss syndrome

    microscopic polyangiitis

    Henoch-Sch#{246}nbein purpura

    essential cryoglobubinemic vasculitis

    cutaneous leukocytoclastic angiitis

    ANCA Small-Vessel Vasculitis 315

    ANCA-SVV typically has an absence or paucity of immu-

    Table 1. Names and definitions of vasculitis adopted by the Chapel Hill Consensus Conference on the Nomenclature of

    Systemic Vasculitisa

    Granubomatous arteritis of the aorta and its major branches, with a

    predilection for the extracranial branches of the carotid artery. Often

    involves the temporal artery. Usually occurs in patients older than 50

    and is often associated with polymyalgia rheumatica.

    Granulomatous inflammation of the aorta and its major branches. Usually

    occurs in patients younger than 50.

    Necrotizing inflammation of medium-sized or small arteries without

    gbomerulonephritis or vasculitis in arterioles, capillaries, or venules.

    Arteritis involving large, medium-sized, and small arteries, and associated

    with mucocutaneous lymph node syndrome. Coronary arteries are often

    involved. Aorta and veins may be involved. Usually occurs in children.

    Granulomatous inflammation involving the respiratory tract, and necrotizing

    vasculitis affecting small- to medium-sized vessels, e.g., capillaries,

    venules, arterioles, and arteries. Necrotizing glomerulonephritis is

    common.

    Eosinophib-rich and granubomatous inflammation involving the respiratory

    tract and necrotizing vasculitis affecting small- to medium-sized vessels,

    and associated with asthma and blood eosinophibia.

    Necrotizing vascubitis with few or no immune deposits, affecting small

    vessels, i.e., capillaries, venubes, or arterioles. Necrotizing arteritis

    involving small- and medium-sized arteries may be present. Necrotizing

    glomerulonephritis is very common. Pulmonary capi!laritis often occurs.

    Vascubitis with immunogbobubin A-dominant immune deposits, affecting

    small vessels, i.e. , capillaries, venules, or arterioles. Typically involves

    skin, gut, and glomeruli, and is associated with arthralgias or arthritis.

    Vasculitis with cryogbobubin immune deposits, affecting small vessels, i.e.,

    capillaries, venules, or arterioles, and associated with cryogbobulins in

    serum. Skin and glomeruli are often involved.

    Isolated cutaneous beukocytoclastic angiitis without systemic vasculitis or

    glomerulonephntis.

    a The ANCA-associated vasculitides are Wegeners granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. (Modified

    from Jennette et al. [I] with permission.).

    Table 2. Approximate frequencies of PR3-ANCA (C-ANCA) and MPO-ANCA (P-ANCA) in patients with

    glomerulonephritis caused by Wegeners granubomatosis (WG), microscopic polyangiitis (MPA), and

    pauci-immune necrotizing and crescentic gbomerubonephritis without systemic vascubitis (NCON)

    ANCA Result WG MPA NCGN

    Positive PR3-ANCAIC-ANCA 65 to 75% 35 to 45% 30 to 40%

    Positive

    Negative

    MPO-ANCA/P-ANCA

    ANCA

    15

    10

    to 25%

    to 20%

    45

    10

    to 55%

    to 20%

    60 to 70%

    10 to 20%

    arteries are affected more often than larger arteries, but a few SVV. Necrotizing leukocytoclastic angiitis in medullary vasa

    patients with ANCA-SVV will have involvement

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