Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of monoclonal protein (M protein) in the blood. M protein is produced by plasma cells in bone marrow. Etiology is unknown. Affected patients may experience peripheral neuropathy and are more likely to experience fractures, osteopenia, or osteoporosis. MGUS is clinically asymptomatic and remains benign in 75% of cases, but 25% of cases progress to myeloma or a B-cell disorder (macroglobulinemia, amyloidosis, and lymphoma). Thus, affected patients must be monitored regularly since the condition can become malignant. MGUS occurs in a little over 3% of white individuals over the age of 50 and is often an incidental finding. In the general population, mean age of diagnosis is in the 70s. Associated conditions include autoimmune disease, chronic viral hepatitis, and certain infections.

Several dermatoses are associated with MGUS including scleromyxedema, primary systemic amyloidosis, and normolipemic plane xanthomas. Additionally, erythema elevatum diutinum, subcorneal pustular dermatosis, scleredema, and acquired angioedema (C1 inhibitor deficiency) may have an underlying monoclonal gammopathy. Schnitzler syndrome and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, multiple myeloma, and skin changes and sclerotic bone changes) are rare syndromes that are seen in the setting of MGUS.