Monoclonal Gammopathy Of Undetermined Significance

MGUS is a premalignant plasma cell disorder with monoclonal protein under 3 g/dL, under 10% clonal marrow plasma cells and no end organ damage.

• Prevalence 3% over 50 years, 5% over 70; more common in Black populations.

• Types: non-IgM (IgG, IgA) MGUS progressing to myeloma, IgM MGUS progressing to Waldenström or lymphoma, light chain MGUS.

• Progression risk about 1% per year; risk factors: non-IgG isotype, M protein over 1.5 g/dL, abnormal free light chain ratio.

• Monoclonal gammopathy of clinical significance (renal, neurological, skin, ocular) requires clone directed therapy.

• Asymptomatic, detected on protein electrophoresis.

• Associated: peripheral neuropathy, scleromyxoedema, Schnitzler syndrome, acquired angioedema, nephropathy, cryoglobulinaemia.

• Osteoporosis, fractures, venous thrombosis risk.

• Serum protein electrophoresis, immunofixation, serum free light chain ratio, quantitative immunoglobulins.

• Full blood count, calcium, creatinine, urinalysis, urine protein electrophoresis.

• Marrow biopsy if high risk (IgA/IgM, M protein over 1.5 g/dL, abnormal light chain ratio) or clinical suspicion.

• Skeletal imaging if symptoms.

• Mayo risk stratification: 0 factors 5% progression at 20 years, 3 factors 58%.

• No treatment; reassurance and education.

• Monitoring: low risk, repeat tests at 6 months then every 2 to 3 years or when symptoms arise; intermediate/high risk, annual or biannual monitoring with blood count, calcium, creatinine, protein electrophoresis, free light chains.

• Refer for new symptoms (bone pain, anaemia, hypercalcaemia, renal impairment, recurrent infection).

• Bone density assessment and treatment of osteoporosis.

• Treat monoclonal gammopathy of clinical significance with clone directed therapy (rituximab, bortezomib-based regimens).

• Avoid unnecessary investigation.