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Paraproteinemia incl Multiple myeloma

A paraprotein is a monoclonal immunoglobulin or light chain present in the blood or urine
 , it is produced by a clonal population of mature B cells , most commonly plasma cells.

Normally serum immunoglobulins are polyclonal and represent the combined yield from millions of different plasma cells.

Individuals > 50 yrs incidence is 3.2 % Varies with age and sex-Elderly > Young , Male > Female Ethnic variation – threefold higher in African Americans than the white population

When to consider checking ? Malaise and fatigue Bone disease- persistent back pain , osteopenia 
or lytic lesions Impaired renal function Normocytic , normochromic anaemia ± pancytopenia Hypercalcaemia Recurrent bacterial infection Hyperviscocity Nephrotic syndrome Cardiac failure Malabsorption Peripheral neuropathies , carpal tunnel syndrome Incidental persistent raised ESR

Complications –Neuropathy Nephrropathy Cytopenias
○ ITP
○ AIHA Cold agglutinins Cryoglobulins

Multiple Myeloma Neoplastic proliferation of plasma cells in the bone marrow and occasionally in other organs as the liver , spleen and lymph nodes. Predominantly affects older adults Accounts for 10 % of all haematological malignancies in UK & 1 % of all malignancies Median age of presentation is 66 yrs with < 3 % of patients being < 40 More in black people , pacific islanders and Maori in New Zealand , low in Asians living in Asia.

Can present with constellation of symptoms – diagnosis can be challenging ( often delayed )

 Presenting features are due to infiltration of malignant plasma cells into the bones or other organs ( eg myelosuppression , hepatosplenomegaly ) and


Paraprotein load – hyperviscocity , peripheral neuropathy or light chains in serum ( eg renal failure due to light chain nephropathy )

Presenting symptoms –Normocytic normochromic anaemia Bone pain Renal impairment Fatigue and weakness Pathological fracture Recurrent infections Remal impairment Acute hypercalcemia Hyperviscocity Neuropathy Spinal cord compression Hepatomegaly Splenomegaly Lymphadenopathy Fever.

Tests to consider –FBC and Blood film ESR or plasma viscosity Us & Es LFT Bone profile Serum immunoglobulins Serum / Urine electrophoresis Serum beta2-microglobulin LDH Skeletal survey

Transplant candidates – based on age and co-morbidities. Options include
Single autologous stem cell transplant
 ( SCT ), Tandem autologous SCT or Allogenic SCT

Monoclonal gammopathy of uncertain significance-Presence of monoclonal protein 
in the serum or urine of an 
individual with no evidence of multiple myeloma , AL amylodosis , Waldenstrom macroglobulinemia or other related disorders 
( Mayo Clinic Group Kyle 1978 )

Asymptomatic elevation of total protein Diagnosis of exclusion Found in about 1 % of people over 50 and in 3 % over 70.About 1.5 % cases of MGUS per year proceed to myeloma ( ie premalignant condition ) Annual f/u with electrophoresis and densitometry to detect increasing paraprotein concentration is recommended ( indicator of possible progression towards myeloma ).In multiple myeloma plasma cells make a clone of itself and these malignant plasma cells or myeloma cells accumlate in the bone marrow. The malignant cells secrete an antibody , called the M protein or M-spike or paraprotein or myeloma protein- these can be detected in blood and or urine of most patients.

References


  1. Management of paraproteinaemia Postgrad Med J. 2007 Apr; 83 ( 978 ) : 217-223
  2. Understanding and Identifying Monoclonal Gammopathies Clinical Chemistry Vol46 , Issue 8 August 2000
  3. Evaluating Paraproteinemia Jeffrey Wolf MD University of California
  4. Multiple myeloma : RACGP from diagosis to treatment Volume 42 , No 10 , October 2013
  5. Essential Haematology AV Haffbrand et al
  6. Oxford Handbook of Clinical Haematology
  7. Paraproteinemias assessed via http://eknygos.lsmuni.lt/springer/582/181-188.pdf Practice >>
  8. Easily Missed ? Mutiple myeloma BMJ 2012 ;344;d7953
  9. GP Online Multiple Myeloma accesses via https://www.gponline.com/multiple-myeloma/haematology/article/1378253
  10. E Medicine Multiple Myeloma Dhaval Shah MD et al May 2016

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