MONOCLONAL GAMMOPATHY OF CLINICAL SIGNIFICANCE

Abstract

Aside from the risk to evolve to MM or WM, or to be associated with AL amyloidosis or POEMS syndrome, the M-protein in persons with MGUS can cause “per se” the so-called “monoclonal gammopathies of clinical significance –MGCS” resulting in neurologic, skin, ocular, bleeding or other disorders. The monoclonal gammopathy of renal significance (MGRS), coined to highlight renal damage, different from cast nephropathy or amyloid deposition, linked to the M-protein is not discussed here. In patients with MGUS and peripheral neuropathy (PN), and no evidence of AL amyloidosis or POEMS, a causal relationship must be considered. In the IgM type, a gammopathy-associated PN is likely (50% are MAG positive) while in the IgG and IgA types a CIDP with coincidental MGUS is the most likely diagnosis. The main skin conditions related to M-proteins are: 1) cryoglobulin (IgG/IgM) vasculatis with petechiae, purpura or ulcers, 2) Schnitzler syndrome (IgM, chronic urticaria, fever, artralgia), 3) pyoderma gangrenosum (IgA, ulcers with central necrosis), 4) necrobiotic xanthogranuloma (IgG, yellow papules, nodules, plaques), 5) escleromixedema (IgG-lambda, mucine dermal deposition with occasional systemic involvement –cardiomyopathy, pulmonary fibrosis or reduced esophageal motility-) or 6) acquired generalized cutis laxa (lambda, elastolysis of the skin –premature ageing-, occasionally associated with kidney –fibrillar glomerulopathy-, heart or lung involvement). The most frequent ocular M-protein related condition is crystalline keratopathy (Ig deposition, corneal thickening, photophobia, visual loss). Bleeding can result from acquired von Willebrand deficiency or by impaired platelet aggregation induced by the M-protein. In summary, The M-protein in MGUS can cause relevant clinical conditions. If a causal relationship is proven or highly suspected, therapy against the plasma cell clone (rituximab-based in IgM-types and bortezomib-based, even including ASCT, in non-IgM) must be timely initiated.