ANCA Small Vessel Vasculitis

A group of patients with small-vessel vasculitis  and glomerulonephritis have serum ANCA; the antibodies are of two types,

anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO).

 ANCA are produced with the help of T cells and activate leukocytes and monocytes, which together damage the walls of small vessels. Endothelial injury also attracts more leukocytes and extends the inflammation.

Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome belong to this group because they are ANCA-positive and have a pauci-immune glomerulonephritis with few immune complexes in small vessels and glomerular capillaries.

 Patients with any of these three diseases can have any combination of the above serum antibodies, but anti-PR3 antibodies are more common in Wegener's and anti-MPO antibodies are more common in microscopic polyangiitis or Churg-Strauss.

While each of these diseases have some unique clinical features, most features do not predict relapse or progression, and as a group they are generally treated in the same way. Only the presence of upper-airway involvement, persistent pulmonary injury, and anti-PR3 antibodies suggests that the course of disease will be more difficult. Induction therapy usually includes some combination of plasmapheresis, methylprednisolone, and cyclophosphamide. The benefit of plasmapheresis in this setting is uncertain. The steroids are tapered soon after acute inflammation subsides, and patients are maintained on cyclophosphamide or azathioprine for up to a year to minimize the risk of relapse.

Wegener's Granulomatosis

Patients with this disease classically present with fever, purulent rhinorrhea, nasal ulcers, sinus pain, polyarthralgias/arthritis, cough, hemoptysis, shortness of breath, microscopic hematuria, and 0.5–1 g/24 h of proteinuria; occasionally there may be cutaneous purpura and mononeuritis multiplex.

Presentation without renal involvement is termed limited Wegener's granulomatosis, although some of these patients will show signs of renal injury later. Chest x-ray often reveals nodules and persistent infiltrates, sometimes with cavities. Biopsy of involved tissue will show a small-vessel vasculitis and adjacent noncaseating granulomas. Renal biopsies during active disease demonstrate segmental necrotizing glomerulonephritis without immune deposits.

 The cause of Wegner's granulomatosis is unknown. In case-controlled studies there is greater risk associated with exposure to silica dust. The disease is also more common in patients with alpha-1 antitrypsin deficiency, which is an inhibitor of PR3.

Microscopic Polyangiitis

Clinically, these patients look somewhat similar to those with Wegener's granulomatosis, except they rarely have significant lung disease or destructive sinusitis. The distinction is made on biopsy where the vasculitis in microscopic polyangiitis is without granulomas. Some patients will also have injury limited to the capillaries and venules.

Churg-Strauss Syndrome 


When small-vessel vasculitis is associated with peripheral eosinophilia, cutaneous purpura, mononeuritis, asthma, and allergic rhinitis, a diagnosis of Churg-Strauss syndrome is considered.

 Hypergammaglobulinemia, elevated levels of serum IgE, or the presence of rheumatoid factor sometimes accompanies the allergic state. Lung inflammation, including fleeting cough and pulmonary infiltrates, often precedes the systemic manifestations of disease by years; lung manifestations are rarely absent. A third of patients may have exudative pleural effusions associated with eosinophils.

 Small-vessel vasculitis and focal segmental necrotizing glomerulonephritis can be seen on renal biopsy, usually absent eosinophils or granulomas. The cause of Churg-Strauss syndrome is autoimmune, but the inciting factors are unknown. Interestingly, some asthma patients treated with leukotriene receptor antagonists will develop this vasculitis.