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Vasculitis is inflammation of blood vessels, often with ischemia, necrosis, and occlusive changes. It can affect any blood vessel—arteries, arterioles, veins, venules, or capillaries. Most damage results when inflammation narrows vessels and causes tissue necrosis. Clinical manifestations of specific vasculitic disorders are diverse and depend on the size of the involved vessels and the organs affected by ischemia.
Etiology
Vasculitis may be primary or secondary. Primary vasculitis results from an inflammatory response that targets the vessel walls and has no known cause. Secondary vasculitis may be triggered by an infection, a drug, or a toxin or may occur as part of another inflammatory disorder or cancer.
Pathophysiology
Histologic description of an affected vessel should include the following:
Certain features (eg, predominant inflammatory cells, location of inflammation) suggest particular vasculitic processes and may aid in the diagnosis (see Table 1: Vasculitis: Histologic Clues to Diagnosis of Vasculitic Disorders ). For example, in many acute lesions, the predominant inflammatory cells are PMNs; in chronic lesions, lymphocytes predominate.
Inflammation may be segmental or involve the entire vessel. At sites of inflammation, varying degrees of cellular inflammation and necrosis or scarring occur in one or more layers of the vessel wall. Inflammation in the media of a muscular artery tends to destroy the internal elastic lamina.
Leukocytoclastic vasculitis is a histopathologic term used to describe findings in small-vessel vasculitis. It refers to breakdown of inflammatory cells that leaves small nuclear fragments (nuclear debris) in and around the vessels. Inflammation is transmural, rarely necrotizing, and nongranulomatous. PMNs predominate early; later, lymphocytes predominate. Resolution of the inflammation tends to result in fibrosis and intimal hypertrophy. Intimal hypertrophy or secondary clot formation can narrow the arterial lumen and accounts for tissue ischemia or necrosis.
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Table 1
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Histologic Clues to Diagnosis
of Vasculitic Disorders
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Findings
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Possible Diagnoses
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Predominantly non-necrotizing granulomatous inflammatory infiltrate with lymphocytes, macrophages, and multinucleated giant cells
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Giant cell arteritis
Primary angiitis of the CNS (certain types)
Takayasu's arteritis
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Fibrinoid vascular necrosis of the vessel wall with a mixed infiltrate consisting of various combinations of leukocytes and lymphocytes
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Churg-Strauss syndrome
Immune complex–associated vasculitis
Microscopic polyangiitis Polyarteritis nodosa
RA
Wegener's granulomatosis
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Granulomatous infiltrate of small and medium-sized vessels with varying degrees of necrosis
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Wegener's granulomatosis
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IgA deposits*
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Henoch-Schönlein purpura
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Scant or complete absence of immunoglobulins and complement deposition in the vessel walls*,†
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Churg-Strauss syndrome
Microscopic polyangiitis
Wegener's granulomatosis
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*Detected using immunofluorescence staining.
†Disorders thus characterized are called pauci-immune vasculitic disorders.
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Classification
Vasculitic disorders can be classified according to the size of the predominant vessel affected. However, there is often substantial overlap (see Table 2: Vasculitis: Classification of Vasculitic Disorders).
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Table 2
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Classification of Vasculitic
Disorders
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Size of Affected Vessels
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Disorders
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Symptoms and Signs
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Large
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Behçet's syndrome
Giant cell arteritis
Polymyalgia rheumatica
Takayasu's arteritis
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Limb claudication
Unequal BP measurements or unequal pulse strength in the limbs
CNS ischemic symptoms (eg, strokes)
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Medium
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Cutaneous vasculitis
Polyarteritis nodosa
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Ischemic lesions leading to tissue infarction in the affected organs, commonly including
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Muscles: Myalgias
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Nerves: Mononeuritis multiplex
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GI tract: Mesenteric ischemia
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Kidneys: New-onset hypertension
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Skin: Ulcers and nodules
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Small
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Churg-Strauss syndrome
Cutaneous vasculitis
Henoch-Schönlein purpura
Microscopic polyangiitis
Wegener's granulomatosis
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Ischemic lesions and commonly affected organs similar to those for medium-sized vessels, except for the following:
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Renal involvement: Usually results in glomerulonephritis
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Skin lesions: More likely to be purpuric
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Leukocytoclastic vasculitis*: Present more often
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*Detected by biopsy of skin lesions.
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Symptoms and Signs
Size of the affected vessels helps determine clinical presentation (see Table 2: Vasculitis: Classification of Vasculitic Disorders).
Regardless of the size of the vessels involved, patients can present with symptoms and signs of systemic inflammation (eg, fever, night sweats, fatigue, anorexia, weight loss, arthralgias, arthritis). Some manifestations are life- or organ-threatening and require immediate treatment. They include alveolar hemorrhage, rapidly progressive glomerulonephritis, mesenteric ischemia, orbital pseudotumor threatening the optic nerve (in Wegener's granulomatosis), and vision loss in patients with giant cell arteritis.
Diagnosis
Systemic vasculitis is suspected in patients with the following:
Primary vasculitic disorders are diagnosed based on the presence of characteristic symptoms, physical findings, compatible laboratory test results, and exclusion of other causes (ie, secondary vasculitis). Histologic examination is done whenever possible and may point to a particular vasculitic disorder (see Table 1: Vasculitis: Histologic Clues to Diagnosis of Vasculitic Disorders).
Routine laboratory tests are done. Most results are nonspecific but can help support the diagnosis. Tests usually include CBC, ESR or C-reactive protein, serum albumin and total protein, and tests for ANCA. Often, patients present with elevated ESR or C-reactive protein, anemia due to chronic inflammation, elevated platelets, and low serum albumin and total protein. Freshly voided urine must be tested for RBCs, RBC casts, and protein to identify renal involvement. Serum creatinine levels should be checked and monitored. Leukopenia and thrombocytopenia are uncommon.
Detection of ANCA may support the diagnosis of Wegener's granulomatosis, Churg-Strauss syndrome, or microscopic polyangiitis. Standardized tests for ANCA include immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining of ethanol-fixed neutrophils can detect the cytoplasmic pattern of cANCA or the perinuclear pattern of pANCA. Then solid-phase ELISA is used to check for antibodies specific for the major autoantigens: proteinase-3 (PR3), which correlates with the cANCA staining pattern, or myeloperoxidase (MPO), which correlates with the pANCA staining pattern. Because false-positives occur, ANCA should be measured only when one of these vasculitic disorders is clinically suspected.
Other useful laboratory tests include hepatitis B and C serologic testing, testing for the presence of cryoglobulins, and complement levels to diagnose viral or cryoglobulinemic vasculitis. Further testing is determined by clinical findings. A chest x-ray should be done to check for infiltrates, but high-resolution noncontrast CT of the chest may be needed to check for subtle findings, such as small nodules or cavities. Bilateral diffuse infiltrates suggest possible alveolar hemorrhage, which requires immediate diagnosis and treatment. Other imaging tests may be required. For example, magnetic resonance angiography of large blood vessels and the aorta is useful for diagnosis and monitoring when such vessels appear affected. If symptoms suggest mononeuritis multiplex, electromyography is done.
Because vasculitic disorders are rare and treatment may have severe adverse effects, tissue biopsy is done to confirm the diagnosis whenever possible. Usually, clinical findings suggest the best site for biopsy. For example, if clinical and electromyographic findings suggest mononeuritis multiplex with dysfunction of a specific peripheral nerve, tissue around arteries supplying the nerve is biopsied. Usually, biopsies of unaffected tissue are much less likely to provide positive results.
Because vasculitis is often segmental or focal, biopsy may not show inflammation even when a vessel is affected. Sampling from multiple areas or long segments of a vessel may increase diagnostic sensitivity.
Treatment
Treatment depends on the etiology and extent and severity of disease. For secondary vasculitic disorders, removing the cause (eg, infection, drug, cancer) can help.
For primary vasculitic disorders, treatment aims to induce and maintain remission. Remission is induced by using cytotoxic immunosuppressants and high-dose corticosteroids, usually for 3 to 6 mo, until remission occurs or disease activity is acceptably reduced. Adjusting treatment to maintain remission usually takes longer, on average > 1 or 2 yr. During this period, the goal is to eliminate corticosteroids or reduce their dose and to use less potent immunosuppressants as long as needed.
Induction of
remission:
For less severe forms of vasculitis, low doses of corticosteroids and less potent immunosuppressants (eg, methotrexate , azathioprine , mycophenolate mofetil ) may be used.
Severe, rapidly progressive and life- or organ-threatening vasculitis (eg, causing alveolar hemorrhage, rapidly progressive glomerulonephritis, or mesenteric ischemia) is a medical emergency requiring hospital admission and immediate treatment. Treatment consists of the following:
Acrolein, a product of cyclophosphamide degradation, is toxic to the bladder epithelium and can lead to hemorrhagic cystitis. For patients who have taken cyclophosphamide long term, risk of cystitis is increased, and some develop transitional cell carcinoma of the bladder. During cyclophosphamide therapy, careful hydration is needed to reduce the risk of bladder hemorrhage, cystitis, and bladder cancer. Mesna binds acrolein and is mixed together with the IV cyclophosphamide infusion. One mg of mesna is added for each milligram of cyclophosphamide . Recurrence of hematuria, especially without casts and dysmorphic red cells, should prompt a referral for urologic evaluation. Cystoscopy and renal imaging should be done to exclude cancer.
Remission maintenance:
Corticosteroids are tapered to zero or to the lowest dose that can maintain remission. Usually, methotrexate (with folate) or azathioprine is prescribed to replace cyclophosphamide because they have a better adverse effects profile. The duration of this treatment varies, from one year to several years. Patients with frequent relapses may need to take immunosuppressants indefinitely.
Long-term use of corticosteroids can have significant adverse effects. Patients who are taking such therapy should be given Ca and vitamin D supplements and bisphosphonates to help prevent or minimize osteoporosis; bone density should be monitored yearly.
Last full review/revision May 2008 by Carmen E. Gota, MD
Content last modified May 2008
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