Makindo Medical Notes

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

Myeloma should be considered in any patient presenting with bone pain, raised calcium, or a high ESR.

About

• A malignant tumour of plasma cells, originating from the B-cell lineage.
• Often produces monoclonal immunoglobulins (IgG, IgA) or light chains.
• Median survival is approximately 2–3 years.

Incidence

• More common in men than in women.
• Incidence: ~5.4 per 100,000 per year.
• About 5,500 new cases per year in the UK.

Stages of Progression

Note: Treatment is not indicated for patients with MGUS (Monoclonal Gammopathy of Undetermined Significance). Randomized trials show no benefit from early intervention; simple monitoring of paraproteins and clinical review is usually sufficient.

Aetiology

• Uncontrolled proliferation of a single clone of plasma cells.
• Bone marrow infiltration leads to bone destruction and cytopenias.
• Suppression of normal immune function causes immunodeficiency.
• Myeloma proteins can lead to hyperviscosity and amyloidosis.
• Renal failure is common, often multifactorial (e.g., light chain damage).
• Anaemia arises from both marrow infiltration and renal insufficiency.

Plasma cell secretions activate osteoclasts, causing bone lysis and pathological fractures, neurological impairment, and hypercalcaemia (which may be exacerbated by renal dysfunction).

Epidemiology

• Twice as common in individuals of African descent.
• Myeloma may develop in ~1% of patients with MGUS.

Differing Manifestations

Clinical Features

• Age >60 years in most cases; slightly higher incidence in males.
• Bone pain from lytic lesions or pathological fractures; vertebral collapse can cause cord compression.
• Renal failure, often linked to Bence–Jones protein (light chains).
• Higher infection risk due to immunoparesis (low normal immunoglobulins).
• Pancytopenia from marrow infiltration.
• Hypercalcaemia causing fatigue, confusion, constipation, polyuria.

AL Amyloid Symptoms

• Peripheral neuropathy, restrictive cardiomyopathy, nephrotic syndrome, severe fatigue.
• Carpal tunnel syndrome, gastrointestinal bleeding/diarrhoea, macroglossia, arrhythmias.
• Hyperviscosity syndrome (especially IgA myeloma) with dizziness, blurred vision, bleeding.

Investigations

• FBC: Anaemia, possible low platelets/WBC.
• Biochemistry: Elevated ESR, CRP, LDH, urate, and hypercalcaemia.
• Renal Function: Impaired in ~50% due to light chain nephropathy.
• Serum Protein Electrophoresis & Urine for BJP: Detect monoclonal protein.
• Bone Marrow Biopsy: Quantifies plasma cell infiltration; FISH for cytogenetics.
• Imaging: Whole-body MRI, CT, PET-CT to identify lesions or plasmacytomas.

CRAB Mnemonic

• Hypercalcaemia: Corrected Ca²⁺ >2.75 mmol/L (or >11 mg/dL).
• Renal impairment: CrCl <40 ml/min or creatinine >177 µmol/L (>2 mg/dL).
• Anaemia: Hb <100 g/L (10 g/dl) or >20 g (2 g/dl) below normal.
• Bone lesions: Lytic lesions or osteoporotic fractures on imaging.

Complications

• Pathological fractures.
• Hypercalcaemia.
• Renal failure.
• Recurrent infections.
• Anaemia.
• Spinal cord compression (~10% of patients).

Beta-2 microglobulin is a useful prognostic marker. Elevated levels and low albumin both indicate a poorer prognosis.

Management

• Younger, Fit Patients: Combinations of bortezomib (Velcade), thalidomide, and dexamethasone, followed by autologous stem cell transplantation (ASCT) if in remission.
• Supportive Care: Blood transfusions for anaemia; IV pamidronate or zoledronic acid for bone pain; adequate hydration for hypercalcaemia.
• Orthopaedic Referral: Procedures like kyphoplasty or vertebroplasty for vertebral fractures.
• Pain Management: NSAIDs (monitor renal function) and appropriate analgesics.
• Hyperviscosity Syndrome: Plasma exchange may be required.
• Allopurinol: Prophylaxis against hyperuricaemia.
• Radiotherapy: For painful lesions or to address cord compression.
• Patient Support: Emotional and palliative support; discuss prognosis and treatment goals.

References

• Guidelines for the Management of Multiple Myeloma