Signs and Symptoms of Multiple Myeloma
Multiple myeloma presents with a constellation of symptoms captured by the CRAB criteria: hypercalcemia, renal insufficiency, anemia, and bone lesions, along with recurrent infections and the presence of monoclonal protein. 1, 2
Cardinal Clinical Features (CRAB Criteria)
Bone Disease
- Bone pain is the most common presenting symptom, typically affecting the thoracic spine, ribs, and long bones 1, 3
- Lytic bone lesions appear on skeletal radiography, whole-body MRI, or PET/CT 1
- Pathologic fractures occur, particularly vertebral compression fractures causing acute back pain 2, 3
- Severe osteopenia may be present even without discrete lytic lesions 2
- Spinal cord compression can develop, potentially leading to paraplegia if untreated 3
Anemia
- Normochromic, normocytic anemia with hemoglobin <10 g/dL or ≥2 g/dL below the lower limit of normal 1, 2
- Presents as weakness, fatigue, and pallor 2
- Results from bone marrow infiltration by malignant plasma cells and suppression of normal hematopoiesis 3
Renal Insufficiency
- Serum creatinine >2 mg/dL or estimated creatinine clearance <40 mL/min 1, 2
- Often presents as mild increases in serum creatinine with or without nonselective proteinuria 2
- Progressive dehydration may occur secondary to hypercalcemia 2
- Can manifest as unexplained renal insufficiency with proteinuria 2
Hypercalcemia
- Serum calcium >11.5 mg/dL 1, 2
- Causes polyuria, gastrointestinal disturbances (nausea, vomiting, constipation), and progressive dehydration 2
- Leads to decreased glomerular filtration rate 2
- May produce neurologic symptoms including drowsiness, confusion, or altered mental status 3
Additional Common Manifestations
Infectious Complications
- Recurrent infections are a hallmark symptom due to immune dysfunction 2, 4
- Patients experience increased susceptibility to bacterial infections 1
- Fever may be a presenting feature 5, 3
Neurologic Symptoms
- Headache, blurring of vision, and vertigo can occur from hyperviscosity syndrome 3
- Cranial nerve involvement (particularly nerves II, V, VI, VII, and VIII) may develop 3
- Peripheral neuropathy can result from monoclonal protein effects 3
- Ataxia, hemiparesis, and epileptiform seizures may occur from metabolic derangements 3
- Spinal cord compression presents with progressive weakness, sensory changes, and bowel/bladder dysfunction 3
Laboratory Abnormalities
- Monoclonal protein (M-protein) ≥3 g/dL in serum or abnormal free light chains in urine 2
- Bone marrow plasma cells ≥10% on aspiration and biopsy 2
- Elevated serum protein on routine testing may be the initial clue 5
Less Common Presentations
Extramedullary Disease
- Hepatomegaly and splenomegaly occur in approximately 5% of cases 6
- Lymphadenopathy develops in 4% of patients 6
- Rarely, myeloma can present clinically mimicking lymphoma with widespread lymphadenopathy and pleuropulmonary involvement 6
Other Manifestations
- Soft tissue plasmacytomas may develop 3
- Biclonal gammopathy occurs in 1% of cases 6
- Carpal tunnel syndrome, orthostatic hypotension, and malabsorption syndrome suggest concurrent AL amyloidosis 2
Critical Diagnostic Pitfalls
Distinguish symptomatic multiple myeloma from its precursor conditions to avoid unnecessary treatment or delayed intervention 1, 7:
- MGUS (Monoclonal Gammopathy of Undetermined Significance): M-protein <3 g/dL, bone marrow plasma cells <10%, no CRAB criteria—requires only observation 1, 7
- Smoldering Multiple Myeloma (SMM): M-protein ≥3 g/dL and/or bone marrow plasma cells ≥10%, but no CRAB criteria—requires monitoring but not immediate treatment 1, 7, 4
- Active Multiple Myeloma: Requires presence of CRAB criteria or specific myeloma-defining biomarkers (≥60% clonal plasma cells, involved/uninvolved free light chain ratio ≥100, or >1 focal lesion on MRI) 1, 8
Consider AL amyloidosis in the differential diagnosis when patients present with substantial albuminuria, congestive heart failure, peripheral neuropathy, or hepatomegaly, as management differs significantly 2