Symptoms Indicating Multiple Myeloma
Multiple myeloma is characterized by specific end-organ damage symptoms known as CRAB criteria: hypercalcemia, renal insufficiency, anemia, and bone lesions, which are the key indicators for diagnosis. 1
Primary Symptoms (CRAB Criteria)
Hypercalcemia: Serum calcium >11.5 mg/dL, which can cause symptoms such as polyuria, gastrointestinal disturbances, progressive dehydration, and decreased glomerular filtration rate 1
Renal insufficiency: Serum creatinine >2 mg/dL or estimated creatinine clearance <40 mL/min, often presenting as mild increases in serum creatinine with or without nonselective proteinuria 1
Anemia: Normochromic, normocytic anemia with hemoglobin <10 g/dL or ≥2 g/dL below the lower limit of normal, manifesting as weakness, fatigue, and pallor 1, 2
Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures, typically presenting as bone pain (especially in the thoracic spine) or pathologic fractures 1, 3
Additional Common Symptoms
Recurrent bacterial infections: Due to impaired immune function from abnormal immunoglobulin production 1
Extramedullary plasmacytomas: Soft tissue masses composed of malignant plasma cells outside the bone marrow 1
Generalized symptoms: Weakness, fatigue, malaise, and weight loss 2, 4
Neurological symptoms: May include spinal cord compression (causing paraplegia), cranial nerve involvement, headache, blurred vision, vertigo, and ataxia 3
Laboratory Abnormalities
Monoclonal protein (M-protein): Presence of M-protein ≥3 g/dL in serum or abnormal free light chains in urine 1, 5
Bone marrow plasma cells: ≥10% clonal plasma cells in bone marrow examination 1, 5
Diagnostic Pitfalls
Distinguishing from other conditions: Many elderly patients have concomitant diseases that can mimic multiple myeloma symptoms 1
Anemia differential: Must be distinguished from iron, vitamin B12, or folic acid deficiency, anemia of chronic disease, or myelodysplastic syndrome 1
Bone lesion differential: A single asymptomatic lytic bone lesion could be a benign bone cyst or angioma rather than myeloma 1
Hypercalcemia differential: Consider coincidental hyperparathyroidism, especially when lytic bone lesions are absent 1
Osteoporosis vs. myeloma: Long-standing progressive osteoporosis with compression fractures suggests a benign process, while sudden onset often indicates active myeloma 1
Distinguishing Multiple Myeloma from Related Conditions
Monoclonal Gammopathy of Undetermined Significance (MGUS): M-protein <3 g/dL, bone marrow plasma cells <10%, and absence of end-organ damage 1, 5
Smoldering Multiple Myeloma (SMM): M-protein ≥3 g/dL and/or bone marrow plasma cells ≥10%, but absence of end-organ damage 1, 5
Primary Systemic Amyloidosis (AL): May present with substantial albuminuria, congestive heart failure, renal failure, peripheral neuropathy, orthostatic hypotension, carpal tunnel syndrome, hepatomegaly, or malabsorption syndrome 1
When to Suspect Multiple Myeloma
Multiple myeloma should be suspected in patients (especially those over 65 years) presenting with unexplained:
- Bone pain with radiographic evidence of lytic lesions 4, 6
- Anemia with other cytopenias 4, 6
- Renal insufficiency with proteinuria 1, 4
- Hypercalcemia 1, 4
- Recurrent infections 1, 2
Early recognition of these symptoms is crucial for timely diagnosis and treatment initiation, which can significantly impact patient outcomes and quality of life 4, 6.