Signs and Symptoms of Multiple myeloma
المؤلف:
Mary Louise Turgeon
المصدر:
Immunology & Serology in Laboratory Medicine
الجزء والصفحة:
5th E, P369-371
2025-09-14
174
The signs and symptoms of MM include bone pain, typically in the back or chest, and weakness, fatigue, and pallor associated with anemia or abnormal bleeding. In all, 20% of patients exhibit hepatomegaly and 5% demonstrate splenomegaly. In some cases, the major manifestations of disease result from acute infection, renal insufficiency, hypercalcemia, or amyloidosis. Weight loss and night sweats are not prominent until the disease is advanced. Bone pain, anemia, and renal insufficiency constitute a triad of signs and symptoms strongly suggestive of MM.
In 1975 a staging system for myeloma was developed. This system defines indolent versus severe disease and determines a basis for therapy. Patients are divided into three groups, with classification based on the production of IgG by plasma cells and the total quantity of IgG in the body. The number of abnormal plasma cells is correlated with the hemoglobin value, serum calcium level, serum IgG peak, and presence or absence of lytic bone lesions. Renal function is also considered an important factor, not only because it is essential to survival, but also because IgG light chains can damage the kidneys.
Some physicians use a simpler system of staging based on serum albumin, hemoglobin, and β2-microglobulin levels.
Skeletal Abnormalities About 90% of patients with MM have broadly disseminated destruction of the skeleton, which is responsible for the pre dominance of bone pain. These abnormalities consist of punched-out lytic areas (Fig. 1), osteoporosis, and fractures in about 80% of patients. The vertebrae, skull, thoracic cage, pelvis, and proximal humeri and femurs are the most frequent sites of involvement.
Fig1. Multiple myeloma. A, Several scattered, small, well-marginated lytic lesions appear in calvarium, located in normally mineralized bone. Multiple lytic lesions can also be seen in the mandible. B, Multiple circumscribed lytic lesions crowd bones throughout skull. Lesions are still discrete and margins of most are fairly sharp. (From Newton TH, Potts DG: Radiology of the skull and brain, St Louis, 1971, Mosby.)
Hematologic Features
The diagnosis of MM depends on the demonstration of an increased number of plasma cells in a bone marrow aspirate and/or biopsy and supporting laboratory results (see later, “Diagnostic Evaluation”). Although the bone marrow is typically involved, the disorder may involve other tissues. For example, a positive correlation exists between the production of osteoclast-activating factor by bone marrow cells and the extent of skeletal destruction. Other hematologic factors contributing to the signs and symptoms of pallor and anemia include bleeding, qualitative platelet abnormalities, inhibition of coagulation factors by M protein, and thrombocytopenia. Intravascular coagulation may occur.
Renal Disorders
Acute renal failure (ARF) occurs in about 5% to 10% of patients. Although ARF may occur at any time in the course of myeloma, it can be the initial manifestation of disease. ARF has been observed after infection, hypercalcemia, dehydration, and IV urography. Serum creatinine levels are elevated in about half these patients and approximately one third have hypercalcemia.
Chronic renal failure is a common development in MM patients. As many as two thirds of patients display serum creatinine levels higher than 1.5 mg/dL and 10% to 20% may develop end-stage renal disease (ESRD). Patients with IgD or light-chain myeloma are much more likely to develop renal failure than those with IgG or IgA myeloma. Proteinuria is a common finding, with over half of all MM patients excreting abnormal amounts of Bence Jones (BJ) protein (light chains). Patients with BJ proteinuria are much more likely to have renal tubular defects than those without BJ proteinuria.
Studies have suggested that BJ proteins have a deleterious effect on renal function via at least two mechanisms. First, renal failure may result from intratubular precipitation of BJ protein and subsequent intrarenal obstruction. When the distal collecting tubules become obstructed by large casts consisting mainly of BJ protein, the disorder may be referred to as myeloma kidney. The second mechanism of renal failure may be a function of direct tubular cell injury. As a result of these tubular defects, abnormalities in urine-concentrating ability and renal acidification are observed. Although the presence of a large concentration of BJ proteinuria is usually associated with some degree of renal dysfunction, some patients excrete large amounts of BJ protein for years and maintain renal function.
Lambda light chains have been implicated in nephrotoxicity, but their role has not been firmly established.
Neurologic Features
Pain is a common characteristic of MM, often caused by com pression of the spinal cord or nerves. Compression produces back pain, with weakness or paralysis of the lower extremities and bowel or bladder incontinence.
Infectious Diseases
The most frequent cause of death is infection. Patients with MM have increased susceptibility to infectious microorganisms because of an inability to cope with bacterial infections and certain viral diseases. Increased susceptibility principally results from defective antibody synthesis caused by the crowding out and suppression of normal plasma cell precursors.
Repeated bouts of sepsis, often resulting from recurrent infection by microorganisms such as pneumococci or gram-negative bacteria, are common. Pneumonia, pyelonephritis, meningitis, and arthritis are the leading forms of sepsis; when bacteremia ensues, mortality is high.
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