Multiple myeloma history and symptoms
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The signs and symptoms of multiple myeloma are most commonly associated with either elevation in calcium concentrations, renal failure, anemia and involvement of the bones such as fractures and pains.
History and Symptoms
Early multiple myeloma does not have any symptoms. In as many as 30-40% cases the diagnosis may be incidental and is often diagnosed on routine blood screening. A rise in total protein levels without a concomitant rise in albumin levels must make the physician suspicious for a possibility of multiple myeloma. As the tumor grows larger, people may notice one or more of the following symptoms:
- Bone pain
- Pathological fractures
- Numbness and/or muscle weakness
- Confusion
- Dizziness
- Edema in legs
- Back pain, numbness, dysthesias suggestive of spinal cord compression.
- Bleeding
- Recurrent infections
Because many organs can be affected by multiple myeloma, the symptoms and signs vary greatly. A mnemonic sometimes used to remember the common tetrad of multiple myeloma is CRAB - C = Calcium (elevated), R =Renal failure, A = Anemia, B = Bone lesions.[1] Multiple myeloma has many possible symptoms, and all symptoms may be due to other causes. They are presented here in decreasing order of incidence.
- Bone pain
Multiple myeloma bone pain usually involves the spine and ribs, and worsens with activity. Persistent localized pain may indicate a pathological bone fracture. Involvement of the vertebrae may lead to spinal cord compression. Multiple myeloma bone disease is due to proliferation of tumor cells and release of IL-6, also known as osteoclast activating factor (OAF), which stimulates osteoclasts to break down bone. These bone lesions are lytic in nature and are best seen in plain radiographs, which may show a "punched-out" resorptive lesions. The breakdown of bone also leads to release of calcium into the blood, leading to hypercalcemia and its associated symptoms.
- Infection
The most common infections are pneumonias and pyelonephritis. Common pneumonia pathogens include S pneumoniae, S aureus, and K pneumoniae, while common pathogens causing pyelonephritis include E coli and other gram-negative organisms. The increased risk of infection is due to immune deficiency resulting from diffuse hypogammaglobulinemia, which is due to decreased production and increased destruction of normal antibodies.
- Renal failure
Renal failure may develop both acutely and chronically. It is commonly due to hypercalcemia (see above). It may also be due to tubular damage from excretion of light chains, also called Bence Jones proteins, which can manifest as the Fanconi syndrome (type II renal tubular acidosis). Other causes include glomerular deposition of amyloid, hyperuricemia, recurrent infections (pyelonephritis), and local infiltration of tumor cells.
- Anemia
The anemia found in multiple myeloma is usually normocytic and normochromic. It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production (hematopoiesis) by cytokines.
- Neurological symptoms
Common problems are weakness, confusion and fatigue due to hypercalcemia. Headache, visual changes and retinopathy may be the result of hyperviscosity of the blood depending on the properties of the paraprotein. Finally, there may be radicular pain, loss of bowel or bladder control (due to involvement of spinal cord leading to cord compression) or carpal tunnel syndrome and other neuropathies (due to infiltration of peripheral nerves by amyloid). It may give rise to paraplegia in late presenting cases.
References
- ↑ International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749-57. PMID 12780789.