Systemic manifestations of monoclonal gammopathy

Systemic manifestations of monoclonal gammopathies (MG) are rare but extremely varied. This general review focuses on the hyperviscosity syndrome, neurological disorders, skin changes, the POEMS syndrome, and biological manifestations, with the exception of amyloidosis AL and cryoglobulinemia. The hyperviscosity syndrome usually involves a combination of general, hemorrhagic, ocular and central neurological disorders. The principal neurological manifestations are peripheral neuropathies, mainly due to IgM with anti-MAG activity. Skin disorders include overload dermatoses (xanthomatosis, mucinosis), neutrophilic dermatosis, urticaria, edema and the AESOP syndrome. The POEMS syndrome classically consists of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasmocyte proliferation, and cutaneous manifestations. MG interference with assay methods can lead to false hyponatremia, hypoglycemia, hyperbilirubinemia, hypercalcemia and hypertransferrinemia. These systemic manifestations can reveal classical MG-related disorders such as monoclonal gammopathy of undetermined significance (MGUS), solitary plasmocytoma, multiple myeloma, and Waldenstrom's disease. They are due either to the chemicophysical properties of the monoclonal immunoglobulin, or to its antibody activity (especially against autoantigens), with potential therapeutic implications.