Overview

Multiple myeloma, like most medical conditions, manifests itself slightly differently in each patient. Because multiple myeloma can affect many organs, several possible symptoms exist, and they vary greatly. No sign or symptom is a direct indicator of multiple myeloma. Any symptom may be due to other causes, and multiple myeloma may initially cause no symptoms at all.

Multiple myeloma occurs when cancerous myeloma cells collect in many bones, unlike a plasmacytoma, which only involves a solid tumor in one bone. Symptoms typically begin to develop when myeloma cells start to crowd the bone marrow and prevent it from generating new healthy blood cells. This leads to a general weakening of the immune system, which can cause fatigue, repeated infections, and more frequent bruising and bleeding. Myeloma cells can also collect on the bones, cause growths, and weaken bones.

Elevated M Proteins

Multiple myeloma is often discovered on a routine blood or urine examination when a doctor finds asymptomatic anemia (see below) or elevated levels of abnormal proteins. These abnormal proteins are usually antibodies or parts of antibodies, collectively called monoclonal (M) proteins. While M proteins made by myeloma cells serve no function, they can build up and thicken the blood, leading to a condition called hyperviscosity syndrome. This causes symptoms such as:

• exhaustion
• headache
• dizziness
• confusion
• trouble walking
• nosebleeds
• vision changes, e.g., blurred vision or bulging eyes
• retinopathy (non-inflammatory damage to the retina)
• pain, tingling, or numbness in the hands, feet, fingers, toes, or other parts of the body

Bone Pain

Bone pain related to multiple myeloma usually affects the spine and ribs, and it typically worsens with activity. Back pain can occur acutely or chronically and can cause weakening of the vertebrae or even collapse of a vertebral body. Persistent localized pain can suggest a bone fracture. Involvement of the vertebrae may lead to spinal cord compression.

Myeloma bone disease is due to proliferation of tumor cells and release of interleuken-6 (IL-6). The IL-6 molecule stimulates osteoclasts, which usually absorb bone tissue during growth or healing, to break down bone. These bone lesions are destructive in nature and are best seen in plain X-rays, which may show “punched-out” lesions. The breakdown of bone also leads to the release of calcium into the blood, leading to hypercalcemia and its associated symptoms.

Hypercalcemia

Hypercalcemia, or an elevated level of calcium in the blood, occurs when calcium from affected or damaged bones dissolves into the blood. Common symptoms associated with hypercalcemia include:

• weakness
• confusion
• fatigue or muscle weakness
• loss of appetite
• nausea or vomiting
• excessive thirst
• frequent urination
• constipation
• mental confusion or trouble thinking
• abdominal cramping
• weight loss
• restlessness
• neurological symptoms

Renal Failure

Renal (kidney) failure is a common result of hypercalcemia, but it may also be due to kidney tubule damage from excretion of light chains. This can manifest as Fanconi syndrome, in which tubule damage leads to impaired functioning of the kidney. Renal failure may develop either acutely or chronically. It usually leads to increased urination.

Anemia

Anemia occurs when cancerous myeloma cells replace healthy, oxygen-carrying red blood cells in bone marrow. In the anemia typical in myeloma patients, the concentration of hemoglobin is usually within normal range. Anemia can lead to:

• fatigue
• pallor
• weakness
• tiredness
• shortness of breath

Infection

A weakened immune system and abnormal immunoglobin proteins can often lead to repeated infections. The most frequent in multiple myeloma patients are pneumonia, pyelonephritis (inflammation of the kidney), bladder or kidney infections, and sinusitis. Common pneumonia pathogens include S. pneumoniae, S. aureus, and K. pneumoniae. Common pathogens causing pyelonephritis include E. coli and other gram-negative organisms.

While increased infection can occur prior to diagnosis, the greatest risk period for infection is in the initial few months after the start of chemotherapy. Some patients may benefit from replacement immunoglobulin therapy to reduce the risk of infection.

Other Possible Symptoms

Other symptoms that have been associated with multiple myeloma include:

• enlarged liver or spleen
• nerve pain
• loss of bowel or bladder control (due to compressed spinal cord or nerves)
• increased level of suppressor T cells
• decreased levels of helper T cells
• weakness or numbness in legs
• paraplegia
• carpal tunnel syndrome and other neuropathies

Diagnosis »