Vasculitis refers generically to inflammation occurring within the walls of blood vessels. Blood vessel inflammation can result in either perforation of affected vessels with hemorrhage into adjacent structures or thrombosis with subsequent ischemia and infarction of supplied tissues. Vasculitis can occur as a primary process or secondary to another connective tissue disease, infection, or drug exposure. The systemic vasculitides are a heterogeneous group of disorders (Table 1) characterized by blood vessel inflammation affecting vessels of varying size and location resulting in a wide range of clinical manifestations dictated largely by which vessels are affected (Fig. 1 and Fig. E2). Vasculitis is traditionally classified according to the size of the blood vessels predominantly affected (Table 2). Antineutrophilic cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA); microscopic polyangiitis (MPA), including renal-limited vasculitis (RLV); and eosinophilic granulomatosis with polyangiitis (EGPA). All are associated with ANCA and have similar features on renal histology (e.g., a focal necrotizing, and often crescentic, pauciimmune glomerulonephritis). Several of these are covered in individual topics, including topics on ANCA-associated vasculitis, giant cell arteritis (GCA), Takayasu arteritis, and Henoch-Schönlein purpura (HSP). Severity varies between and within specific vasculitides from a relatively benign, self-limited process to severe, life-threatening multisystem organ involvement with significant morbidity and mortality.

Figure 1 Major categories of noninfectious vasculitis.

Not included are vasculitides that are known to be caused by direct invasion of vessel walls by infectious pathogens, such as rickettsial vasculitis and neisserial vasculitis. EGPA, Eosinophilic granulomatous polyangiitis; GPA, granulomatous polyangiitis; HSP, Henoch-Schönlein purpura.

From Freehally J et al: Comprehensive clinical nephrology, ed 6, Philadelphia, 2019, Saunders.

• The epidemiology and demographics of the various vasculitides vary by the individual disease and, where applicable, are covered under the relevant vasculitis disease chapters.
• The most common form of systemic vasculitis in the U.S. is giant cell arteritis, with an approximate incidence of 170 cases/1 million per year in individuals older than 50 yr.
• ANCA-associated vasculitis is significantly less common with aggregate incidence estimated at ∼20 per million in the U.S.
• Polyarteritis nodosa (PAN) has an annual incidence of 1/100,000 persons but has a higher incidence in patients with existing hepatitis B or C infections.
• Age distribution can demonstrate significant variability between the vasculitides as shown by the fact that GCA generally does not occur before age 50, whereas 90% of cases of HSP occur in the pediatric population, and 80% of patients with Kawasaki disease are under age 5.
• Although genetic factors clearly play a role in disease susceptibility, familial cases of vasculitis are rare.

• Clinical presentation often includes nonspecific constitutional symptoms including fever, malaise, headache, and weight loss.
• Signs and symptoms are generally dictated by the tropism of involved vessels.
• Skin manifestations of vasculitis include petechiae, palpable purpura (Fig. E3), subcutaneous nodules, livedo reticularis, ulcerations, and digital ischemia.
• Kidney involvement of medium-sized and large vessel vasculitis is often in the form of renovascular hypertension. Glomerulonephritis may be seen in small vessel vasculitis.
• Pulmonary small vessel involvement can cause alveolar hemorrhage, which can present with cough, dyspnea, and alveolar hemorrhage.
• Organ involvement in polyarteritis nodosa is summarized in Table 3.
• Mononeuritis multiplex is the characteristic finding of vasculitis affecting the vasa nervorum of the peripheral nervous system.
• GI involvement of the mesenteric vasculature can cause postprandial pain, bleeding, and perforation.
• Testicular pain or tenderness can be seen with hepatitis B infection in PAN.
• Cardiac involvement can include chest pain secondary to ischemic infarcts in the coronary arteries, pericarditis, cardiomyopathy, and arrhythmias.
• Arthritis, while nonspecific, can be present.
• Significant clinical variability exists between the various vasculitides, although overlapping symptoms may be seen.

Most forms of systemic vasculitis are of unknown etiology. Cryoglobulinemia vasculitis is often secondary to hepatitis C infection, and cutaneous leukocytoclastic vasculitis is often related to a drug exposure.

• Infective endocarditis
• Atrial myxoma
• Cholesterol emboli
• Malignancy
• Hypercoagulopathy
• Congenital collagen vascular disorder

• The diagnosis of most forms of systemic vasculitis relies on the history and physical examination as well as supportive laboratory testing. Table 4 describes differential diagnostic features of selected forms of small vessel vasculitis.
• Tissue biopsy is important in establishing an accurate diagnosis; biopsy sites should target affected tissues.
• Electromyography and nerve conduction studies can evaluate for site of nerve or muscle involvement before biopsy in patients with neuropathy or myopathy.
• Imaging such as mesenteric angiography can be supportive and may obviate the need for tissue biopsy.

• Laboratory markers of systemic inflammation include elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and anemia of chronic disease.
• ANCA targeting myeloperoxidase (MPO) and proteinase 3 (PR3) are frequently found in several small vessel vasculitides, including GPA (Wegener), microscopic polyangiitis (MPA), and EGPA (Churg-Strauss).
• Hepatitis C antibodies and rheumatoid factor are often present in cryoglobulinemic vasculitis.
• Positive hepatitis B serologies are commonly found in PAN.
• Urinalysis in patients with glomerulonephritis due to small vessel ANCA-associated vasculitis will generally demonstrate hematuria with active urinary sediment, with red blood cell casts and proteinuria.

• CT angiography, magnetic resonance angiography, and angiography can demonstrate vascular narrowing and aneurysm formation in suspected medium-size and large-vessel vasculitis.
• Pulmonary and sinus CT scans can demonstrate active pulmonary and upper airway disease in ANCA-associated vasculitis.

• Systemic corticosteroids are generally required to gain initial control of active vasculitis, although mild cases of drug-induced cutaneous leukocytoclastic vasculitis often require cessation of the offending medication and at times, low-dose corticosteroid use.
• HSP and vasculitis limited to the skin, including cutaneous PAN, can often be managed without further immunosuppression.
• Major organ-threatening disease in systemic vasculitis has traditionally required pulse steroids and oral or intravenous cyclophosphamide for induction of remission.
• Studies have demonstrated noninferiority of rituximab compared to cyclophosphamide in ANCA-associated vasculitis with major organ involvement, and it is approved for this use.
• Rituximab with prednisone has also been shown to be effective in the treatment of relapsing flares of disease activity in ANCA-associated vasculitis.
• Less severe disease such as GPA limited to the upper airways can be managed with methotrexate rather than cyclophosphamide.
• Trimethoprim-sulfamethoxazole should be used to prevent Pneumocystis jiroveci infection with concurrent immunosuppressive therapy.
• The goal of acute therapy is to induce remission of disease activity and is generally continued for 1 to 2 mo once this is achieved, at which point chronic therapy is used.

• The goal of chronic therapy is to prevent disease relapse and minimize medication side effects.
• Steroids are gradually tapered as allowed by disease activity.
• Immunomodulatory agents such as methotrexate or azathioprine are commonly used for maintenance therapy in place of cyclophosphamide to reduce side effects.
• Cryoglobulinemic vasculitis due to chronic hepatitis C virus infection will often improve with treatment of the underlying viral infection.
• In PAN with concurrent hepatitis B infection, appropriate antiviral treatment (interferon alpha-2b or lamivudine with or without plasma exchange) is indicated.
• Rituximab may also be an appropriate remission maintenance agent in ANCA-associated vasculitis. For GPA or MPA, scheduled redosing of rituximab every 4 to 6 mo is conditionally recommended over redosing based on ANCA titers or CD19 B-cell counts.

Varies widely among the various vasculitides

Systemic vasculitis care is generally coordinated by a rheumatologist. Renal, pulmonary, neurology, and GI consultations are often needed when vasculitis involves these organ systems. Isolated cutaneous leukocytoclastic vasculitis is often managed by dermatology.

Cogan Syndrome (Related Key Topic)

Cryoglobulinemia (Related Key Topic)

Giant Cell Arteritis (Related Key Topic)

ANCA-Associated Vasculitis (Related Key Topic)

IgA Vasculitis (Related Key Topic)

Kawasaki Disease (Related Key Topic)

Takayasu Arteritis (Related Key Topic)