Schnitzler syndrome is a rare autoinflammatory disorder associated with immunoglobulin M (IgM) or, less frequently, IgG monoclonal gammopathy. Schnitzler syndrome typically manifests with an urticarial eruption, intermittent fever, arthralgias, myalgias, and bone pain in around 40% of patients. Other manifestations include angioedema, lymphadenopathy, and hepatosplenomegaly. There is slight male predominance, and onset occurs on average early in the sixth decade. Due to the rarity of this condition (approximately 300 cases reported worldwide), the diagnosis is often delayed for years.

The pathogenesis of Schnitzler syndrome remains unclear, although it is thought to be an acquired autoinflammatory disorder in which increased interleukin (IL)-1b and IL-6 leads to loss of anti-inflammatory Th17 cell properties. The role of the paraprotein is unknown, although increased IL-1 stimulation could contribute to IgM paraproteinemia.

Schnitzler syndrome may progress to Waldenström macroglobulinemia or other lymphoproliferative disorders. Waldenström disease is the most common complication, occurring in 15% of cases after 10-20 years of symptom onset. As with several other autoinflammatory conditions, ongoing inflammation leads to production of hepatic acute phase reactants, including serum amyloid A protein, which can lead to AA amyloidosis. Overall prognosis depends on whether this progression to hematologic dyscrasia or secondary amyloidosis occurs.