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Emergency and Acute Medicine – Multiple Myeloma
Multiple myeloma is a malignant disorder arising from transformation of normal hematopoietic stem cells into clonal plasma cells. These abnormal myeloma cells proliferate within the bone marrow, leading to extensive marrow infiltration, bone destruction, and suppression of normal blood cell production. The disease is characterized by several pathologic derangements, including immunodeficiency, anemia, renal dysfunction, and skeletal damage. Plasma cell secretions stimulate osteoclast activity, resulting in bone lysis, pathologic fractures, neurologic compromise, and hypercalcemia, which is often worsened by concurrent renal impairment.
Immunodeficiency in multiple myeloma develops through multiple mechanisms. Normal immunoglobulin production is suppressed, and both T- and B-cell function are impaired. Granulocytopenia and reduced cell-mediated immunity further increase susceptibility to infection. Abnormal monoclonal proteins produced by myeloma cells contribute to hyperviscosity syndromes, amyloidosis, and renal injury. Light chains may accumulate within renal tubules, causing progressive nephron destruction and eventual renal failure. Common complications of the disease include recurrent infections, anemia, hypercalcemia, renal failure, pathologic fractures, and spinal cord compression, which occurs in approximately 10% of patients.
The incidence of multiple myeloma is approximately 4 per 100,000 individuals, accounting for about 1% of all cancers and 15% of hematopoietic malignancies. The mean age at diagnosis is around 70 years, with a slightly higher incidence in men and African Americans. The disease is rare in younger populations, with fewer than 2% of cases occurring in patients under 40 years of age.
Bone pain is the most common presenting symptom and typically involves the ribs, sternum, spine, clavicle, skull, shoulders, or hips. This pain may lead to reduced mobility or neurologic deficits if vertebral involvement is present. Constitutional symptoms such as fatigue, weakness, weight loss, anemia, and recurrent infections are also common. Approximately 20% of patients are asymptomatic at diagnosis, with the condition discovered incidentally during routine laboratory testing. Recurrent episodes of severe infection, particularly from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus species, are a major cause of morbidity.
Initial emergency evaluation includes a complete blood count, erythrocyte sedimentation rate, electrolytes, renal function tests, and urinalysis. Imaging should be directed by symptoms, with plain radiographs or skeletal surveys used to evaluate bone pain and detect lytic lesions or fractures. CT or MRI is indicated when pain persists despite normal radiographs or when spinal cord compression is suspected. Diagnostic confirmation relies on serum and urine protein electrophoresis and immunofixation to identify monoclonal proteins, along with bone marrow biopsy demonstrating increased plasma cells.
Laboratory findings often reveal normocytic, normochromic anemia, thrombocytopenia, elevated ESR, hypercalcemia, and renal insufficiency. Peripheral blood smears may show rouleaux formation. Imaging commonly demonstrates lytic bone lesions or compression fractures, while MRI is preferred for detecting spinal cord involvement or soft-tissue plasmacytomas. Bone scans may be falsely negative due to the uncoupling of bone resorption and formation in multiple myeloma.
Emergency management focuses on identifying and treating life-threatening complications. Patients presenting with back pain or neurologic deficits should be presumed to have a pathologic spinal fracture and immobilized appropriately. Hypercalcemia requires aggressive intravenous hydration and bisphosphonate therapy. Renal failure, sepsis, anemia, and spinal cord compression require prompt recognition and intervention. Pain control is essential, with opioid analgesics preferred, as NSAIDs may worsen renal dysfunction. Pathologic fractures should be splinted, and spinal fractures immobilized.
Definitive treatment involves hematology and oncology consultation. Early or asymptomatic disease may not require immediate therapy, as chemotherapy has not shown benefit in early stages. Standard treatment regimens include melphalan and prednisone, which provide symptom relief and reduction of monoclonal protein levels in many patients. Alternative therapies include cyclophosphamide-based regimens, combination chemotherapy, and high-dose chemotherapy with stem cell transplantation. Novel agents such as thalidomide may be used in refractory cases.
Hospital admission is indicated for patients with uncontrolled pain, acute renal failure, severe hypercalcemia, sepsis, spinal cord compression, hyperviscosity syndromes, or other life-threatening complications. Patients whose pain is controlled with oral medications and who have no acute complications may be discharged with close follow-up. All patients should be referred to oncology regardless of disease stage, and neurosurgical or orthopedic consultation is warranted for persistent vertebral pain or instability that may benefit from vertebroplasty or kyphoplasty.
A key clinical pitfall is failure to recognize infectious complications, which remain the leading cause of mortality in multiple myeloma. Febrile illness in these patients should prompt early empiric antimicrobial therapy. Persistent bone pain, unexplained anemia, renal dysfunction, or neurologic symptoms in elderly patients should raise suspicion for multiple myeloma and prompt appropriate evaluation.
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