What are the symptoms of multiple myeloma?

Symptoms of Multiple Myeloma

Multiple myeloma typically presents with the CRAB criteria: hypercalcemia, renal insufficiency, anemia, and bone lesions, along with bone pain, weakness, fatigue, and recurrent infections. 1

Primary Clinical Manifestations

CRAB Criteria (End-Organ Damage)

Hypercalcemia (serum calcium >11.5 mg/dL):

• Polyuria and gastrointestinal disturbances 1
• Progressive dehydration 1
• Muscle weakness and fatigue 2
• Can progress to decreased glomerular filtration rate 1

Renal Insufficiency (serum creatinine >2 mg/dL or creatinine clearance <40 mL/min):

• Often presents as mild increases in serum creatinine 1
• May occur with or without nonselective proteinuria 1
• Present in 20-50% of myeloma patients at diagnosis, typically from light chain cast nephropathy 2

Anemia (hemoglobin <10 g/dL or ≥2 g/dL below normal):

• Normochromic, normocytic pattern 3, 1
• Manifests as weakness, fatigue, and pallor 1
• Present in approximately 73% of patients at diagnosis 4

Bone Lesions:

• Lytic lesions, severe osteopenia, or pathologic fractures 3, 1
• Typically presents as bone pain or pathologic fractures 1
• Osteolytic bone disease present in 79% of patients at presentation 4
• Most commonly affects the thoracic spine, causing compressive fractures 5

Constitutional and Systemic Symptoms

Bone Pain:

• The most common presenting symptom 5, 6, 7
• Particularly affects the spine and ribs 5
• May be accompanied by muscle pain 2

Weakness and Fatigue:

• Among the most frequent presenting symptoms 6, 7
• Related to anemia, hypercalcemia, and disease burden 2

Recurrent Infections:

• Common symptom due to immune suppression 1
• Results from suppression of normal hematopoiesis 5

Weight Loss:

• Frequently reported symptom 7

Neurologic Manifestations

Spinal Cord Compression:

• Can lead to paraplegia as the most disastrous sequel 5
• Results from vertebral involvement with osteolytic changes and extradural spread 5

Cranial Nerve Involvement:

• Cranial nerves II, V, VI, VII, and VIII most often affected 5
• Can occur from skull myeloma 5

Metabolic Neurologic Symptoms:

• Headache, blurred vision, drowsiness 5
• Vertigo, ataxia, hemiparesis 5
• Epileptiform seizures 5
• Precoma and coma in severe cases 5
• Related to uremia, hypercalcemia, or hyperviscosity 5

Peripheral Neuropathy:

• Sensorimotor peripheral neuropathy can occur 7

Additional Clinical Features

Hyperviscosity Syndrome:

• Can cause neurologic symptoms and visual disturbances 5

Nephrotic Syndrome:

• May present with substantial albuminuria 1

Orthostatic Hypotension:

• Can occur, particularly in patients with amyloidosis 7

Macroglossia:

• Occurs in 10% of patients with associated primary amyloidosis 7

Important Clinical Pitfalls

The International Myeloma Society emphasizes that unexplained renal insufficiency with proteinuria should raise suspicion for multiple myeloma 1. The combination of any CRAB criteria symptoms, particularly if unexpected or unexplained, should prompt immediate diagnostic evaluation 6. Approximately 98% of patients have a monoclonal protein (M-protein) in serum or urine at diagnosis 7, making this a key laboratory finding alongside clinical symptoms. Acute kidney injury is present in 19% of patients at presentation 4, making renal symptoms particularly important to recognize early.