Small Vessel Vasculitis

ANCA-Associated Vasculitis

Antineutrophil cytoplasmic antibodies (ANCA) are defined by indirect immunofluorescence performed on neutrophils with 2 patterns of staining observed: cytoplasmic (c-ANCA) or perinuclear (p-ANCA). c-ANCA are targeted to serine proteinase-3 (PR3); whereas, p-ANCA positivity indicates antibodies mostly against myeloperoxidase (MPO). The ANCA-associated vasculitides affect small- to medium-sized vessels and do not involve immune complex deposition (“pauci-immune”). The diagnostic value of ANCA testing is well established, but antibody titers do not correlate with disease activity.

Granulomatosis with Polyangiitis (Wegener Granulomatosis)

Granulomatosis with polyangiitis (GPA) predominantly affects the upper and lower respiratory tracts and, in most cases, the kidneys. GPA may present in an indolent manner or be rapidly progressive. Constitutional symptoms include fever and weight loss. Upper airway involvement includes otitis media, nasal ulcers, saddle-nose deformity, sinusitis and subglottic stenosis. Pulmonary manifestations include hemoptysis, cough, fleeting pulmonary infiltrates and bilateral, occasionally cavitary, pulmonary nodules. Limited GPA refers to the absence of renal involvement. Glomerulonephritis occurs in up to 80% of patients and is suggested by the findings of urine red blood cell casts, hematuria, and proteinuria. Up to 40% of patients ultimately develop chronic renal insufficiency. The detection of a positive c-ANCA is 95% specific and has a sensitivity of 90% in patients with active GPA. Diagnosis is best established by lung or kidney biopsy. Treatment of GPA requires a combination of glucocorticoids and daily oral cyclophosphamide. Newer studies have shown efficacy of rituximab as an alternative to cyclophosphamide. Plasma exchange is used as adjunctive therapy with life-threatening disease. Although about 90% of patients achieve remission, up to 30% will relapse, requiring maintenance therapy with an immunosuppressant.

Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing small vessel vasculitis with eosinophilic infiltration that occurs in the setting of antecedent asthma, allergic rhinitis and sinusitis. Patients present with migratory pulmonary infiltrates, mononeuritis multiplex, necrotizing crescentic glomerulonephritis, palpable purpura, cardiomyopathy and gastrointestinal disease. Peripheral eosinophilia occurs in the prodromal stages. Only 40% of patients will be p-ANCA-positive; therefore, biopsy is frequently necessary. Limited cases respond well to glucocorticoid therapy alone, but addition of cyclophosphamide is needed with kidney involvement (azotemia, proteinuria >1 g/day), cardiomyopathy, gastrointestinal disease, or neurologic manifestations. Full remission is achieved in 80% to 90% of patients.

Microscopic Polyangiitis

Microscopic polyangiitis (MPA) is a necrotizing vasculitis, which frequently presents with rapidly progressive glomerulonephritis and pulmonary capillaritis. Pulmonary manifestations range from mild dyspnea and anemia to massive alveolar hemorrhage, with patchy to diffuse infiltrates noted on chest radiography. Similar to other ANCA-associated vasculitides, arthralgias, myalgias, and fever are common, along with palpable purpuric skin lesions. p-ANCA is present in 60% to 85% of patient. The diagnosis is best made by biopsy of skin, kidney, or lung lesions. Combined therapy with glucocorticoids and cyclophosphamide (or rituximab) is used to induce remission, but risk of relapse is high.