The presence of antiproteinase 3 (PR3) antibodies will be diagnostic in this patient who most likely has granulomatosis with polyangiitis (formerly known as Wegener granulomatosis), a systemic necrotizing vasculitis that predominantly affects the upper and lower respiratory tract and kidneys. More than 70% of patients have upper airway manifestations such as sinusitis or nasal, inner ear, or laryngotracheal inflammation. Purpura and ulcers are common skin manifestations. Mononeuritis multiplex may also occur. Pulmonary manifestations can present as cough, hemoptysis, and pleurisy. Characteristic radiographic findings include multifocal infiltrates or nodules, some of which may cavitate; diffuse opacities are seen in patients with pulmonary hemorrhage. Pauci-immune glomerulonephritis occurs in up to 80% of patients. Diagnosis is best established by lung or kidney biopsy. However, the presence of anti-PR3 antibodies is sufficient to establish a diagnosis in patients with classic upper airway manifestations, pulmonary infiltrates/nodules, and urinary abnormalities consistent with glomerulonephritis.

Anti–double-stranded DNA antibodies are specific but relatively insensitive for systemic lupus erythematosus (SLE). SLE is an unlikely diagnosis in this patient because the involvement of the upper airways, particularly with erosion of the sinuses, is uncommon in SLE, the disease is much less common in men than women, and complement levels are typically reduced during active disease.

Antimyeloperoxidase antibodies reflect the presence of ANCA in a perinuclear rather than cytosolic pattern and are associated with microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome), and rapidly progressive glomerulonephritis. However, the presence of upper airway disease essentially rules out these conditions in this patient.

Serum cryoglobulins can be elevated in cryoglobulinemia, which can characteristically affect the kidneys, skin, and nerves and can less commonly affect the lungs. However, upper airway involvement is uncommon, and the normal complement levels, especially a normal C4, also argue against cryoglobulinemia as a diagnosis.