Monoclonal gammopathy of clinical significance: what the rheumatologist needs to know

Monoclonal proteins can provide important information on the diagnosis of several non-malignant systemic inflammatory disorders. At low concentration, they most commonly represent monoclonal gammopathy of undetermined significance (MGUS), whereas high concentrations often signify plasma cell myeloma or B-cell lymphoma. However, several rare inflammatory conditions associated with variable concentrations of monoclonal proteins, systemic symptoms, and organ dysfunction also exist. These conditions are termed monoclonal gammopathies of clinical significance (MGCS). Patients with MGCS might present to rheumatologists with undiagnosed systemic inflammatory disorders and the monoclonal protein provides an important, underappreciated clue for diagnosis. In this Review, we provide an approach to distinguishing MGCS from MGUS and lymphoid neoplasms, focusing on four rare MGCS that rheumatologists must recognise: scleromyxedema, Schnitzler's syndrome, idiopathic systemic capillary leak syndrome (also known as Clarkson's disease), and telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting (known as TEMPI) syndrome.