What are the common symptoms of multiple myeloma?

Multiple Myeloma Symptoms

Multiple myeloma presents with a constellation of symptoms captured by the CRAB criteria: hypercalcemia, renal insufficiency, anemia, and bone lesions, with approximately 75% of patients having anemia, 79% having osteolytic bone disease, and 19% having acute kidney injury at diagnosis. 1, 2

Primary Clinical Manifestations

Bone-Related Symptoms

• Bone pain is the most common presenting symptom, occurring in the majority of patients, typically affecting the thoracic spine and other weight-bearing areas 3, 4, 5
• Pathological fractures occur due to osteolytic lesions, with vertebral compression fractures being particularly common 3
• Skeletal abnormalities are present on imaging in approximately 80% of patients at diagnosis 6
• Pain may be severe enough to require radiotherapy or surgical intervention in cases of vertebral collapse 3

Hematologic Manifestations

• Anemia is present in approximately 75% of patients at diagnosis, characterized as normochromic and normocytic with hemoglobin <10 g/dL or ≥2 g/dL below the lower limit of normal 3, 1
• Weakness, fatigue, and pallor are the typical clinical manifestations of anemia 1, 4, 6
• Anemia occurs in almost all patients with uncontrolled disease 3

Renal Manifestations

• Renal insufficiency is defined as serum creatinine >2 mg/dL or creatinine clearance <40 mL/min and is present in approximately one-fourth of patients at diagnosis 3, 1, 6
• Patients may present with unexplained renal insufficiency with proteinuria 1
• Progressive dehydration and decreased glomerular filtration rate can occur secondary to hypercalcemia 1

Metabolic Manifestations

• Hypercalcemia (serum calcium >11.5 mg/dL) causes polyuria, gastrointestinal disturbances, progressive dehydration, and decreased glomerular filtration rate 3, 1
• Neurologic symptoms from hypercalcemia include drowsiness, confusion, and in severe cases, precoma or coma 5

Additional Clinical Features

Infectious Complications

• Recurrent infections are common due to immune dysfunction from abnormal immunoglobulin production 1, 4
• Fever may be present in some patients 4, 6

Neurologic Manifestations

• Peripheral neuropathy can occur, though it is less common as a presenting feature 5
• Spinal cord compression may develop from vertebral involvement, potentially leading to paraplegia if untreated 3, 5
• Cranial nerve involvement (particularly nerves II, V, VI, VII, and VIII) can occur with skull lesions 5
• Headache, blurring of vision, vertigo, ataxia, and rarely seizures may result from metabolic complications or hyperviscosity 5

Other Systemic Symptoms

• Weight loss is frequently reported 6
• Macroglossia occurs in approximately 10% of patients, particularly those with associated amyloidosis 6

Important Diagnostic Considerations

A monoclonal protein (M-protein) is detectable in serum or urine in approximately 98% of patients at diagnosis, making it a critical laboratory finding 6. The combination of unexplained bone pain, anemia, renal insufficiency, or recurrent infections—particularly when occurring together—should prompt immediate evaluation for multiple myeloma 1, 4.

Common pitfall: Symptoms may be nonspecific initially, and the diagnosis can be delayed if clinicians do not maintain a high index of suspicion when patients present with combinations of these findings, especially in older adults 4, 2.