Measurement of serum cryoglobulin levels is most likely to establish the diagnosis of cryoglobulinemic vasculitis. This patient presents with palpable purpura, glomerulonephritis (elevated serum creatinine, active urine sediment with cellular casts), mononeuritis, and skin infarctions of the fingers and ears. Although several vasculitic diseases may present with this picture, the presence of ear infarctions is most consistent with a diagnosis of cryoglobulinemia. Moreover, low C4 with a normal (or relatively unaffected) C3, in the presence of rheumatoid factor and a monoclonal paraprotein (the rheumatoid factor itself), is the classic pattern for cryoglobulinemic vasculitis. Thus, the test most likely to establish the diagnosis is a serum cryoglobulin level. Because more than 90% of patients with essential mixed cryoglobulinemia are infected with hepatitis C virus, this patient should be screened and treated for this infection.

Anti–cyclic citrullinated peptide antibodies are found in patients with rheumatoid arthritis (RA). Because this patient lacks arthritis, this diagnosis can be excluded, with the rheumatoid factor (also associated with RA) explained by the patient's cryoglobulinemia.

Anti–glomerular basement membrane antibodies can produce glomerulonephritis but would be less likely to cause the skin findings that are seen in this patient and would be inconsistent with the other serologies presented.

Antinuclear antibodies are present in nearly all patients with systemic lupus erythematosus, a disease of protean manifestations that could indeed present in this manner. However, the presence of a normal C3 with a low C4 is atypical in lupus.

p-ANCA is found in several forms of vasculitis, all of which may involve the kidneys and the skin. However, external auricular involvement is not classic, and the C4 is not reduced.