“Paraproteins”/ “M-proteins” are abnormal immunoglobulins produced by clonal plasma cells. They can be intact immunoglobulins (usually IgG, IgA or IgM) or parts of immunoglobulins (usually light chains, very rarely heavy chains). The light chains are assayed in serum (“serum free light chains”, SFLC) or in urine (“Bence Jones proteins”, BJP).
Haematological diseases associated with paraproteins
1) Monoclonal gammopathy of uncertain significance (MGUS)
3% of over-70s and 5% of over the age of 80s have paraproteins which are frequently found incidentally and not associated with symptoms or physical findings.
The overall risk of MGUS progression to myeloma is around 1% per year – this remains constant over time.
3) Low grade Non-Hodgkin Lymphoma can have IgM or IgG paraproteins
4) Rarely seen with CLL and amyloidosis
Who to refer to haematology urgently:
Any new paraprotein or SFLC ratio >100 with accompanying features suggestive of multiple myeloma or other haematological malignancy:
- hypercalcaemia • unexplained renal impairment
- urinary BJP • bone pain or pathological fracture
- radiological lesions reported as suggestive of myeloma
- unexplained anaemia or other cytopenia
- hyperviscosity symptoms (headache, visual loss, acute thrombosis)
Patients with suspected spinal cord compression should be referred in line with the MSSC pathway; if myeloma is suspected discussion with the on call Haematologist by GP or receiving clinician urgently is helpful.
Any patient with a paraprotein not meeting with the above criteria can be discussed with haematology via Advice and guidance. Patients may not need a referral.
Who not to refer to haematology:
Patients with raised immunoglobulin levels in the absence of a monoclonal paraprotein band on serum electrophoresis
Polyclonal gammopathy implies a non-specific immune reaction and is not associated with underlying haematological disorders
- Patients with raised kappa and raised lambda light chains but a normal SFLC ratio (provided neither kappa or lambda light chains individually exceed 100mg/l). These cases are likely representative of inflammatory or infective conditions
- SFLC ratio >0.1 but <5 with no associated intact paraprotein. These cases typically reflect renal impairment or inflammatory or infective conditions
Discharge policy for patients with MGUS
Patients with uncomplicated or low level paraproteins (mostly IgG or IgA with relatively normal SFLC ratio) may be discharged to community monitoring after completing a period of initial investigation
If follow up of paraprotein in primary care is advised, the frequency will be specified in the letter discharging the patient from clinic. If not specified, monitor FBC, renal function and corrected calcium and serum protein electrophoresis and serum free light chains every six months for the first year and then annually.
Dipstick urine for protein annually
- No specific dietary advice required
- Administer all usual vaccines (Flu, Pneumovax etc).
Reasons to re-refer:
- New bone pain or pathological fracture
- Hb <100g/L or 20g/L below baseline with no blood loss and normal haematinics
- >25% increase in creatinine without other causes
- >25% increase in calcium or calcium >2.75 mmol/L without other causes
- Paraprotein increase by >25% and total increase of at least 5g/L
- SFLC (either kappa or lambda) increase by >50% and absolute value of either is >100mg/l
- In cases of IgM paraprotein, re-refer patients with new weight loss, night sweats, fever, lymphadenopathy or organomegaly, or new symptoms of hyperviscosity