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Microscopic Polyangiitis (MPA)
Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels. It may begin as a pulmonary-renal syndrome with rapidly progressing glomerulonephritis and alveolar hemorrhage, but the pattern of disease depends on the organs affected. Diagnosis is made by clinical findings and sometimes confirmed by biopsy. Treatment, which depends on disease severity, includes corticosteroids and immunosuppressants.
MPA is rare (about 13 to 19 cases/million). Pathogenesis is unknown. MPA affects small vessels and is pauci-immune (ie, immune globulin deposition is not seen on tissue biopsy), similar to granulomatosis with polyangiitis (GPA, formerly known as Wegener granulomatosis—see Granulomatosis with Polyangiitis (GPA)) and eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome—see Eosinophilic Granulomatosis with Polyangiitis (EGPA)), which differentiates it from immune complex-mediated small-vessel vasculitides (eg, immunoglobulin A–associated vasculitis—formerly known as Henoch-Schönlein purpura) and small-vessel cutaneous vasculitis. MPA affects predominantly small vessels (including capillaries and postcapillary venules), unlike polyarteritis nodosa, which affects medium-sized muscular arteries (see Polyarteritis Nodosa (PAN)). Older literature (ie, before 1994) did not adequately distinguish between polyarteritis nodosa and MPA―alveolar hemorrhage and glomerulonephritis can occur in MPA but not in polyarteritis nodosa. Rarely, MPA can occur in association with hepatitis B.
Clinical manifestations resemble those of GPA except that granulomatous destructive lesions (eg, pulmonary cavitary lesions) are absent and the upper respiratory tract is usually affected minimally or not at all. In both disorders, antineutrophil cytoplasmic antibodies (ANCA) may be present.
Usually, a prodromal illness with systemic symptoms of fever, weight loss, myalgia, and arthralgia occurs. Other symptoms depend on which organs and systems are affected:
Renal: The kidneys are affected in up to 90% of patients. Hematuria, proteinuria (sometimes > 3 g/24 h), and RBC casts are present. Without prompt diagnosis and treatment, renal failure may follow rapidly.
Cutaneous: About one third of patients have a purpuric rash at the time of the diagnosis. Nail bed infarcts and splinter hemorrhages may occur; digital ischemia occurs rarely.
Respiratory: If the lungs are affected, alveolar hemorrhage may occur and may be followed by pulmonary fibrosis. Rapid-onset dyspnea and anemia, with or without hemoptysis and bilateral patchy infiltrates (seen on chest x-ray) may be due to alveolar hemorrhage, a medical emergency that requires immediate treatment. Mild symptoms of rhinitis, epistaxis, and sinusitis may occur; however, if the upper respiratory tract is severely affected, the cause is more likely to be GPA.
GI: GI symptoms include abdominal pain, nausea, vomiting, diarrhea, and bloody stools.
Neurologic: If the nervous system is affected, mononeuritis multiplex that affects peripheral or cranial nerves usually occurs. Rarely, cerebral hemorrhage, infarction, seizures, or headache results from cerebral vasculitis.
Cardiac: Rarely, the heart is affected.
Ocular: If the eyes are affected, episcleritis usually results.
Microscopic polyangiitis should be suspected in patients who have unexplained combinations of fever, weight loss, arthralgias, abdominal pain, alveolar hemorrhage, new-onset nephritic syndrome, new-onset mononeuritis multiplex, or polyneuropathy. Laboratory tests and sometimes x-rays are done, but the diagnosis is usually confirmed by biopsy.
Tests include CBC, ESR, C-reactive protein, urinalysis, serum creatinine, and tests for ANCA. ESR, C-reactive protein levels, and WBC and platelet counts are elevated, reflecting systemic inflammation. Anemia of chronic disease is common. An acute drop in Hct suggests alveolar hemorrhage or hemorrhage in the GI tract. Urinalysis (to check for hematuria, proteinuria, and cellular casts) should be done, and serum creatinine should be measured periodically to check for renal involvement.
Immunofluorescence staining can detect ANCA; this test is followed by an enzyme-linked immunosorbent assay (ELISA) to check for specific antibodies. At least 60% of patients are ANCA-positive, usually perinuclear ANCA (p-ANCA) with antibodies against myeloperoxidase.
Biopsy of the most accessible involved tissue should be done to confirm vasculitis. Renal biopsy may detect focal segmental pauci-immune necrotizing glomerulonephritis with fibrinoid necrosis of the glomerular capillary wall, leading to formation of cellular crescents.
In patients with respiratory symptoms, chest x-ray is done to check for infiltrates. Bilateral patchy infiltrates suggest alveolar hemorrhage even in patients without hemoptysis.
If patients have dyspnea and bilateral infiltrates, bronchoscopy should be done immediately to check for alveolar hemorrhages and to exclude infection. Blood coming from both lungs and all bronchi, with more blood coming as the bronchoscope goes deeper in the airways, indicates active alveolar hemorrhage. Hemosiderin-laden macrophages appear within 24 to 72 h after onset of hemorrhage and may persist for up to 2 mo.
Treatment is similar to that of GPA. Cyclophosphamide given daily plus corticosteroids improves survival when vital organs are affected. Rituximab has been shown to be noninferior to cyclophosphamide for inducing remission of severe disease. However, data are missing for patients with very high levels of creatinine. Induction and maintenance regimens vary, and adjunctive therapies such as plasma exchange and pulse IV methylprednisolone may or may not need to be used. If patients have impaired renal function due to severe renal involvement or severe alveolar hemorrhage, plasma exchange can be done and may have additional benefit.
Less severe cases may be managed with corticosteroids plus azathioprine or methotrexate.
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