What are the symptoms of multiple myeloma?

Symptoms of Multiple Myeloma

Multiple myeloma presents with a constellation of symptoms primarily characterized by hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB features), which are the hallmark manifestations of end-organ damage caused by the proliferation of malignant plasma cells. 1, 2

Core Clinical Manifestations (CRAB Features)

Bone Disease

• Bone pain: Most common symptom, particularly affecting the back, ribs, and pelvis 3
• Lytic bone lesions: Present in nearly 80% of patients at diagnosis 4
• Pathologic fractures: Especially vertebral compression fractures leading to height loss
• Severe osteopenia: Can occur even without discrete lytic lesions

Hematologic Abnormalities

• Anemia: Present in approximately 73% of patients 5
• Weakness and fatigue: Common presenting symptoms due to anemia 4
• Increased susceptibility to infections: Due to immune dysfunction

Renal Manifestations

• Renal insufficiency: Present in about 25% of patients at diagnosis (creatinine ≥2 mg/dL) 4
• Primary causes: "Myeloma kidney" (cast nephropathy) and hypercalcemia 4
• Proteinuria: May be present due to light chain excretion

Metabolic Disturbances

• Hypercalcemia: Can lead to:
  • Constipation
  • Confusion
  • Dehydration
  • Somnolence
  • Coma in severe cases 3

Neurological Manifestations

• Spinal cord compression: Due to vertebral collapse or extramedullary plasmacytomas
• Peripheral neuropathy: Can occur due to amyloid deposition or as a paraneoplastic phenomenon
• Cranial nerve involvement: Particularly affecting II, V, VI, VII, and VIII cranial nerves 3

Less Common Presentations

• Extramedullary plasmacytomas: Soft tissue masses of malignant plasma cells
• Hyperviscosity syndrome: Visual disturbances, neurological symptoms, bleeding
• Amyloidosis: Can present with:
  • Macroglossia (10% of cases)
  • Nephrotic syndrome
  • Congestive heart failure
  • Orthostatic hypotension
  • Sensorimotor peripheral neuropathy 4

Important Diagnostic Considerations

The diagnosis of symptomatic multiple myeloma requires:

• ≥10% clonal plasma cells in bone marrow or a biopsy-proven plasmacytoma
• Evidence of end-organ damage (CRAB criteria) attributable to the plasma cell disorder 1

CRAB Criteria Defined:

• C: Hypercalcemia (serum calcium >11.5 mg/dL)
• R: Renal insufficiency (serum creatinine >2 mg/dL or creatinine clearance <40 mL/min)
• A: Anemia (hemoglobin <10 g/dL or ≥2 g/dL below lower limit of normal)
• B: Bone lesions (lytic lesions, severe osteopenia, or pathologic fractures) 1, 2

Clinical Pitfalls

1. Differential diagnosis: CRAB features are not exclusive to multiple myeloma; they can be seen in other conditions like diffuse large B-cell lymphoma 6

2. Comorbidities in elderly patients: Several conditions can mimic myeloma manifestations:

   • Mild renal insufficiency due to diabetes or hypertension
   • Anemia due to nutritional deficiencies or chronic disease
   • Diffuse osteoporosis due to age or hormonal changes
   • Hypercalcemia due to hyperparathyroidism 1

3. Distinguishing between MGUS, smoldering myeloma, and symptomatic myeloma: Requires careful evaluation of M-protein levels, bone marrow plasma cell percentage, and presence of end-organ damage 1

Multiple myeloma should be suspected in any patient over 60 years with unexplained anemia, renal failure, hypercalcemia, or bone pain, especially when accompanied by an elevated ESR, low albumin/globulin ratio, or unexplained back pain 2.