Makindo Medical Notes

Related Subjects: |Hypercalcaemia |Multiple Myeloma |Extramedullary Plasmacytoma |Smouldering Myeloma |MGUS |Waldenstrom Macroglobulinaemia |Oncological emergencies

⚠️ Production of a monoclonal IgM can have widespread systemic effects. Waldenström Macroglobulinaemia (WM) is the classic syndrome — a lymphoplasmacytic lymphoma characterised by secretion of IgM paraprotein. It is important to distinguish WM from MGUS and multiple myeloma.

📖 About

• Seen mainly in the elderly (median age ~65–70 years).
• Classified as a lymphoplasmacytic lymphoma with excess monoclonal IgM production.
• Much rarer than myeloma, but clinically significant due to hyperviscosity and immune complications.

🧬 Aetiology

• Driven by malignant proliferation of B cells that differentiate into plasma cells producing monoclonal IgM.
• Often associated with MYD88 L265P mutation (seen in ~90% of WM cases).

🩺 Clinical Features

• Anaemia → fatigue, pallor.
• Hyperviscosity syndrome → headaches, blurred vision, dizziness, epistaxis (nosebleeds), and retinal vein engorgement on fundoscopy.
• Immunological effects → Raynaud’s phenomenon ❄️, peripheral neuropathy, cold agglutinin disease.
• Organ involvement → splenomegaly, hepatomegaly, lymphadenopathy, skin infiltration, GI disturbance.

🔎 Differentials

• Multiple myeloma (usually IgG or IgA, lytic bone lesions common, renal impairment more prominent).
• Monoclonal gammopathy of uncertain significance (MGUS) (no symptoms, lower IgM levels, no marrow infiltration).

⚠️ Complications of Monoclonal IgM

• Raynaud phenomenon (cryoglobulinaemia type I/II).
• Cold agglutinin haemolysis.
• Coagulation abnormalities (bleeding tendency due to IgM binding clotting factors).
• Peripheral neuropathies (antibody-mediated).
• Primary amyloidosis (light chain deposition).
• Tissue deposition of IgM in skin, GI tract, kidneys, and other organs → organ dysfunction.

🧪 Investigations

• FBC: Anaemia, thrombocytopenia, leukopenia.
• ESR: Markedly elevated due to high IgM.
• Serum protein electrophoresis: Sharp IgM M-protein spike.
• Bone marrow: Lymphoplasmacytic infiltrate.
• Fundoscopy: "Sausaging" of retinal veins in hyperviscosity.
• Molecular: MYD88 L265P mutation (diagnostic marker).

💊 Management

• Supportive: IV fluids, transfusions as required.
• Hyperviscosity syndrome → urgent plasmapheresis (immediate relief).
• First-line therapy: Rituximab (anti-CD20) often combined with chemotherapy (e.g. bendamustine, fludarabine).
• Targeted therapy: Ibrutinib (BTK inhibitor) especially in MYD88-mutated WM.
• Stem cell transplantation: Considered in younger/fitter patients with refractory disease.

📚 References

• UpToDate – Waldenström Macroglobulinaemia
• NHS – Waldenström’s Macroglobulinaemia