Information ⬇
Editors
MarjattaSinisalo
OutiLaine
Waldenström's Macroglobulinaemia (WM)
Essentials
- Remember Waldenström's macroglobulinaemia as a rare cause of a increased ESR.
- In most cases a long-term disease; progression may be very slow
- Basically a lymphoma disease (lymphoplasmacytic lymphoma); defined as WM when paraprotein of IgM class is detected
- Clinical picture is characterized by symptoms of cytopenias and immunodeficiency, by extramedullary tumour infiltrates and by hyperviscosity symptoms, often neuropathy.
- No osteolytic lesions
Definition
- Clonal proliferation of mature B cells (differentiation at the lymphocyte-plasma cell level) with a homogeneous immunoglobulin fraction (paraprotein, M component) detected in serum protein electrophoresis. This always consists of IgM.
Epidemiology
- Far less frequent than myeloma, incidence about 0.3 new cases/100 000 persons/year
- Usually occurs in persons aged 60-70 years, very rare in younger persons.
- Slightly more common in men (60% of the cases).
Aetiology
- Unknown; an association of chronic immunostimulation and autoimmune diseases with the disease onset has been suspected.
Diagnostic criteria
- Lymphoplasmacytic lymphoma as a finding in the bone marrow and a serum IgM paraprotein.
Differential diagnosis
- Other conditions with IgM paraprotein:
- IgM-MGUS (monoclonal IgM-gammopathy of undetermined significance, drawing the line between IgM-MGUS and WM is difficult)
- Extremely rare IgM myeloma (osteolytic bone lesions suggest myeloma)
- B-lymphocytic neoplasms (chronic lymphatic leukaemia, diffuse lymphoma)
Clinical picture and laboratory findings
- Each symptom occurs in about 20-25% of the patients
- Deteriorated general condition
- Bleeding
- Splenomegaly
- Hepatomegaly
- Lymphadenopathy
- Symptoms related to hyperviscosity: visual disturbances, headache, dizziness and other symptoms related to cerebral circulation
- Neurological symptoms: distal symmetric slowly-progressing sensorimotor polyneuropathy
- Laboratory findings
- High ESR
- Paraprotein in serum protein electrophoresis which in immunofixation is typed as IgM
- Increased serum viscosity can be detected in about 50% of the patients, if IgM > 40 g/l (the investigation is rarely needed in follow-up, obtaining the result involves a delay).
- Often anaemia or thrombocytopenia
- High paraprotein concentration may cause erratic laboratory test results (e.g. sodium, creatinine, urea, cholesterol, bilirubin, LD, CRP).
Primary investigations
- Complete automated blood count and bone marrow aspiration
- Serum protein electrophoresis (immunofixation should be performed if paraprotein is detected)
- Plasma IgG, IgA and IgM
- Plasma creatinine and serum urate
- Chest x-ray and upper abdominal ultrasonography
Course of the disease and prognosis
- The course of the disease varies greatly; the average life expectancy is 5-6 years. Good response to therapy improves the prognosis.
- WM usually is a long-lasting disease and its progression may be very slow.
Complications
- Hyperviscosity syndrome (usually associated witha high IgM concentration, > 50 g/l)
- Cryoglobulinaemia
- Chronic cold agglutination disease: IgM paraprotein may act as a cold agglutinin and cause haemolytic anaemia.
- Haemorrhages and infections
- An asymptomatic patient is not treated.
- The treatment lines are defined by a specialist in internal medicine or a haematologist.
- Hyperviscosity syndrome is treated with plasmapheresis.
- Treatment of asymptomatic patients is not worthwhile. The following drugs are used in the treatment of symptomatic patients:
- In aggressive disease it is possible to use stem cell transplantation.
Evidence Summaries ⬆