User Tools

Site Tools

Action disabled: revisions

monoclonal gammopathy of uncertain significance (MGUS)


  • the most common (2/3rds of all cases) of a spectrum of diseases called plasma cell dyscrasias which also includes multiple myeloma
  • occurs in around 3% of those aged 50-60yrs, 5% of those aged > 70yrs, and in 10-15% of those aged over 80yrs
  • occurs in 80% of those with the rare systemic capillary leak syndrome
  • cases involve IgG or IgA monoclonal cell populations, 15-20% are IgM
  • patients with MGUS or those with “smouldering myeloma” criteria are conservatively treated, monitored, and should NOT have chemotherapy
  • in contrast, multiple myeloma, which is almost always preceded by MGUS, is lethal and generally requires chemotherapy


  • usually an unexpected finding in the workup of patients for other conditions
  • the presence of a monoclonal immunoglobulin (Ig), also called an M-protein, in the serum or urine
  • diagnostic criteria for MGUS:
    • serum M-protein level <3 g/dL
    • bone marrow plasma cells <10% and low level of plasma cell infiltration in a trephine biopsy specimen
    • no evidence of B-cell proliferative disorder (ie, MM, Waldenström macroglobulinemia, amyloid light-chain amyloidosis)
    • no M-protein or only small amounts of monoclonal light chain in urine
    • no osteolytic lesions, anaemia, hypercalcaemia, or M-protein–related renal function impairment
  • “smouldering myeloma” criteria:
    • as for MGUS BUT:
      • serum M-protein level >3 g/dL, or,
      • 10-20% bone marrow plasma cells


  • some patients with MGUS may progress to less benign disorders if a second mutation event occurs (risk is around 1% each year for IgG and IgA forms, and 1.5% each year for IgM form), such as:
    • multiple myeloma if IgG and IgA MGUS
    • light-chain multiple myeloma if light-chain MGUS
    • Waldenström macroglobulinemia or other lymphoproliferative disorders if IgM MGUS
  • risk factors for progression:
    • abnormal FLC ratio of less than 0.26 or more than 1.65
    • M-protein concentration of > 1.5 g/dL
    • reduction of one or two non-involved Ig isotype levels
  • patients have a higher risk of developing deep venous thrombosis (DVT) (perhaps around 13% develop VTE), especially if:
    • PH or FH DVT
    • immobility
    • low serum albumin level
    • high leukocyte count
  • patients have a mildly increased risk of:
    • spine or rib fractures (RR ~1.6)
    • bacterial and viral infections (RR ~2) - especially if M-protein concentrations over 2.5 g/dL
  • some syndromes of polyneuropathies are associated with MGUS:
    • 10% of patients referred for idiopathic peripheral neuropathy have a monoclonal gammopathy, most commonly MGUS
    • paraproteinaemic demyelinating neuropathy (PDN) syndromes with IgM MGUS is the best characterised one and often includes leg ataxia, areflexia and sensory deficits
    • less commonly, axonal degeneration neuropathy may also occur, more likely with IgG or IgA forms, and usually as a milder, symmetric, slowly progressive, predominantly sensory neuropathy, usually limited to the leg but unlike the demyelinating form, much less responsive to immunomodulating Rx 1)
    • IgG and IgA MGUS have less clearcut causal associations

Mx of patients with MGUS

  • consider measures to reduce risk of VTE, infections, osteoporosis, etc if at higher risk
  • monitor for progression to multiple myeloma, etc:
    • repeat serum electrophoresis at 3 months after 1st diagnosis, then if stable, every 6 months
    • patients should be made aware that transformation to multiple myeloma may be abrupt and they should seek attention if they become symptomatic
mgus.txt · Last modified: 2021/06/13 10:22 by gary1