20-21: Microscopic Polyangiitis

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

Microscopic polyangiitis is a pauci-immune nongranulomatous necrotizing vasculitis that (1) affects small blood vessels (capillaries, venules, or arterioles), (2) often causes glomerulonephritis and pulmonary capillaritis, and (3) is often associated with ANCA on immunofluorescence testing (directed against MPO, a constituent of neutrophil granules). Because microscopic polyangiitis may involve medium-sized as well as small blood vessels and because it tends to affect capillaries within the lungs and kidneys, its spectrum overlaps those of both polyarteritis nodosa and granulomatosis with polyangiitis.

In rare instances, medications, particularly propylthiouracil, hydralazine, allopurinol, penicillamine, minocycline, and sulfasalazine, induce a systemic vasculitis associated with high titers of p-ANCA and features of microscopic polyangiitis.

CLINICAL FINDINGS

A. Symptoms and Signs

A wide variety of findings suggesting vasculitis of small blood vessels may develop in microscopic polyangiitis. These include “palpable” (or “raised”) purpura and other signs of cutaneous vasculitis (ulcers, splinter hemorrhages, vesiculobullous lesions).

Microscopic polyangiitis is the most common cause of pulmonary-renal syndromes, being several times more common than anti–glomerular basement membrane disease. Pulmonary hemorrhage may occur with pathologic findings typically of capillaritis. Interstitial lung fibrosis that mimics usual interstitial pneumonitis may be part of the presenting condition and conveys a poor prognosis.

Vasculitic neuropathy (mononeuritis multiplex) is also common in microscopic polyangiitis.

B. Laboratory Findings

Three-fourths of patients with microscopic polyangiitis are ANCA-positive, usually with anti-myeloperoxidase antibodies (MPO-ANCA) that cause a p-ANCA pattern on immunofluorescence testing. ANCA directed against proteinase-3 (PR3-ANCA) can also be observed.

Elevated acute-phase reactants are typical of active disease. Microscopic hematuria, proteinuria, and RBC casts in the urine may occur. The kidney lesion is a segmental, necrotizing glomerulonephritis, often with localized intravascular coagulation and the observation of intraglomerular thrombi upon renal biopsy.

DIFFERENTIAL DIAGNOSIS

Distinguishing this disease from granulomatosis with polyangiitis may be challenging. Microscopic polyangiitis is not associated with the chronic destructive upper respiratory tract disease often found in granulomatosis with polyangiitis. As noted, a critical difference between the two diseases is the absence of granulomatous inflammation in microscopic polyangiitis. Because their treatments may differ, microscopic polyangiitis must also be differentiated from polyarteritis nodosa.

TREATMENT

Microscopic polyangiitis is usually treated in the same way as granulomatosis with polyangiitis: patients with severe disease, typically involving pulmonary hemorrhage and glomerulonephritis, require urgent induction treatment with corticosteroids and either cyclophosphamide or rituximab. If cyclophosphamide is chosen, it may be administered either in an oral daily regimen or intravenous. Following successful induction of remission, maintenance treatment should be ...