Clinical Presentation of Multiple Myeloma (Bence Jones Disease)
Patients with multiple myeloma (Bence Jones disease) most commonly present with bone pain (particularly in the back, ribs, and pelvis), fatigue from anemia, and recurrent infections due to immunosuppression. 1, 2
Cardinal CRAB Features
The classic presentation follows the CRAB criteria, which define symptomatic disease requiring treatment:
- Hypercalcemia: Corrected serum calcium >11.5 mg/dL (>2.9 mmol/L), manifesting as constipation, confusion, polyuria, and weakness 2, 3
- Renal insufficiency: Serum creatinine >2 mg/dL or creatinine clearance <40 mL/min, often caused by light chain cast nephropathy or hypercalcemia 2, 4
- Anemia: Hemoglobin <10 g/dL or >2 g/dL below normal, presenting as fatigue, weakness, and dyspnea—present in approximately 75% of patients at diagnosis 1
- Bone lesions: Lytic lesions on skeletal imaging (present in 79-80% of patients), causing severe bone pain, pathological fractures, and vertebral collapse 2, 5, 6
Skeletal Manifestations
Bone disease is the hallmark of multiple myeloma and the most frequent presenting symptom:
- Severe bone pain, particularly in weight-bearing bones (vertebrae, ribs, pelvis, proximal femora and humeri) 1, 5
- Pathological fractures from osteolytic destruction without reactive bone formation 7, 6
- Vertebral compression fractures leading to height loss and spinal cord compression 1
- Hypercalcemia from excessive bone resorption 5, 3
Hematologic and Immunologic Features
Anemia is nearly universal and multifactorial:
- Normochromic, normocytic anemia from bone marrow infiltration by plasma cells 1
- Erythropoietin deficiency in patients with renal impairment 1
- Direct apoptosis of erythroblasts induced by myeloma cells 1
Recurrent infections occur due to:
- Immunoparesis (reduction in normal immunoglobulins) despite elevated monoclonal protein 8
- Neutropenia from disease or treatment 1
- Secondary immunodeficiency 8
Bence Jones Protein-Specific Features
In Bence Jones myeloma specifically (representing light chain-only disease):
- Monoclonal free light chains detected in urine (median 0.49 g/24h) without intact immunoglobulin secretion 8
- Paraproteinemia detectable in serum in 86% of cases by sensitive methods 8
- Higher frequency of renal involvement due to light chain toxicity 9, 4
- Elevated serum free light chains (κ-FLC median 4358 mg/L, λ-FLC median 2225 mg/L) with abnormal κ/λ ratio 8
Additional Clinical Manifestations
- Hyperviscosity syndrome: Rare, but can cause bleeding, visual disturbances, and neurologic symptoms 9
- Peripheral neuropathy: From paraprotein deposition or treatment-related toxicity 1
- Amyloidosis: In some cases with light chain deposition causing organ dysfunction 9, 4
- Thrombotic complications: Venous thromboembolism risk varies by treatment regimen (1-16%) 1
Critical Diagnostic Pitfall
CRAB features are not pathognomonic for multiple myeloma. Other malignancies, particularly diffuse large B-cell lymphoma, can present identically with hypercalcemia, renal dysfunction, anemia, and bone lesions 10. Always confirm diagnosis with bone marrow biopsy showing ≥10% clonal plasma cells and monoclonal protein detection by serum/urine protein electrophoresis, immunofixation, or serum free light chain assays 2, 4, 11.