Symptoms of Multiple Myeloma

Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. Because these abnormal plasma cells accumulate and interfere with normal hematopoiesis and bone metabolism, clinical manifestations are often diverse and nonspecific—leading to frequent delays in diagnosis. Common presenting symptoms reflect the classic “CRAB” criteria: hyperCalcemia, Renal insufficiency, Anemia, and Bone lesions.

Patients frequently report persistent bone pain—most commonly in the spine or ribs—due to lytic bone lesions that weaken skeletal integrity and predispose to pathologic fractures. Fatigue and exertional shortness of breath are hallmark signs of anemia, resulting from bone marrow infiltration and cytokine-mediated suppression of erythropoiesis. Hypercalcemia, driven by osteoclast activation and excessive bone resorption, may manifest as nausea, constipation, polyuria, confusion, or even altered mental status in severe cases.

Renal impairment occurs in up to 50% of patients at diagnosis and stems primarily from cast nephropathy—caused by the precipitation of monoclonal free light chains in renal tubules—as well as hypercalcemia and dehydration. Recurrent infections, particularly encapsulated bacterial infections such as pneumonia and sinusitis, arise from hypogammaglobulinemia and impaired humoral immunity. Less common but clinically significant features include peripheral neuropathy (often linked to amyloid deposition or treatment toxicity), hyperviscosity syndrome (in cases with very high paraprotein levels), and bleeding diathesis due to platelet dysfunction or coagulopathy.

Because early-stage disease may be asymptomatic—detected only incidentally through routine blood work—clinicians must maintain a high index of suspicion in older adults presenting with unexplained anemia, recurrent fractures, or progressive renal dysfunction. Timely recognition and comprehensive evaluation—including serum protein electrophoresis, free light chain assay, bone marrow biopsy, and skeletal imaging—are essential for accurate staging and initiation of appropriate therapy.