CRAB

Symptoms of Multiple Myeloma Acronym

Author: Emily Miao, MD, PharmD

Editor: Alyssa Haag, MD

Editor: Lily Guo, MD

Editor: Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator: Jannat Day

Modified: Jan 06, 2025

What is multiple myeloma?

Multiple myeloma is a cancer of the plasma cell (i.e., a specific type of white blood cell of the B cell lineage that produces antibodies) of the bone marrow. Multiple myeloma belongs to a family of plasma cell disorders, which are either acquired or inherited disorders resulting in excess production of a single type of antibody (e.g., immunoglobulins). In multiple myeloma, the abnormal plasma cells produce an excess amount of a specific protein called M protein, which accumulates in the bone marrow and interferes with bone marrow function. Multiple myeloma can either be acquired (e.g., due to exposure to radiation therapy) or be caused by genetic mutations, like the translocation of the immunoglobulin heavy chain on chromosome 14 and the cyclin D1 gene on chromosome 11.

Signs and symptoms include hypercalcemia or elevated calcium in the blood, renal dysfunction, anemia (i.e., decreased healthy red blood cells), and bone pain secondary to bone lesions. The diagnosis is confirmed with urine and blood tests showing elevated monoclonal protein levels measurement along with a bone marrow biopsy. Imaging modalities such as computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) can also identify characteristic lytic bone lesions. Treatment consists of chemotherapy (e.g., bortezomib, lenalidomide-dexamethasone, melphalan); immunomodulators; bisphosphonates to prevent bone loss; antibiotics for acute infection; and glucocorticoids for hypercalcemia. Stem cell transplants, which involve transplanting healthy donor stem cells to replace the recipient’s abnormal bone marrow cells have the potential to cure the condition. Additionally, enrolling in clinical trials for chimeric antigen receptor T cell (CAR-T) therapy in multiple myeloma may be an option for individuals who have refractory disease and have relapsed on four or more prior lines of treatment. CAR-T involves collecting T cells from an individual, and re-engineering them in the laboratory to produce proteins on their surface called “chimeric antigen receptors.” When these chimeric T cells are re-infused into the individual, they are then able to recognize and bind to cancer cells effectively.

There is a pre-malignant form of multiple myeloma, a condition called monoclonal gammopathy of undetermined significance (MGUS). Individuals with MGUS are asymptomatic and have blood monoclonal protein measurements less than 3 g/dl. Because MGUS is a pre-malignant form and 25% of individuals progress to multiple myeloma, routine monitoring is necessary to ensure it is detected early.

An infographic detailing the symptoms of multiple myeloma acronym, CRAB.

What is CRAB?

CRAB is an acronym that highlights the clinical signs and symptoms associated with multiple myeloma.

What does the “C” in CRAB mean?

The “C” in CRAB refers to the development of hypercalcemia. In multiple myeloma, the excess plasma cells often invade the bones in the back, ribs, and hips, which can cause bone pain and loss of bone density. When bones are damaged by plasma cells, osteoclasts (i.e., a specialized type of macrophage) resorb bone tissue, releasing calcium into the blood. Symptoms of hypercalcemia are nonspecific and may include excessive thirst and urination, constipation, nausea, and vomiting. Treatment for hypercalcemia includes intravenous fluids and bisphosphonates (e.g., zoledronic acid) which inhibit osteoclasts’ role in bone resorption and prevent osteoporosis. If left untreated, individuals may develop bone fractures.

What does the “R” in CRAB mean?

The “R” in CRAB refers to renal dysfunction which occurs as a result of the damage caused by excess monoclonal proteins (e.g., kappa and lambda light chains) being filtered through the renal glomeruli. Glomeruli are a tiny network of blood vessels in the kidneys that are responsible for filtering extra fluid and waste from the blood. Because the monoclonal proteins are extremely small, they can pass through renal glomeruli and end up in the tubules or collecting systems of the kidneys. These proteins are toxic to renal tubules and can cause kidney damage and kidney problems. Over time, the kidney’s filtering capacity may be diminished and the pores of the glomeruli will allow larger proteins to pass through.

If these monoclonal immunoglobulins deposit in the kidneys, individuals may also develop a condition called immunoglobulin light chain amyloidosis, which is a rare disease where there is a build-up of a specific amyloid protein in an organ. It causes further renal dysfunction and sometimes, renal failure which requires hemodialysis. Moreover, the increased amount of cancerous cells in the kidney can also lead to overproduction and excretion of uric acid, causing kidney stones, which cause severe acute pain in the abdomen and flanks. Treatment is mainly supportive and strategies are aimed at slowing the rate of multiple myeloma disease progression.

What does the “A” in CRAB mean?

The “A” in CRAB refers to anemia, due to the decreased production of red blood cells. Multiple myeloma leads to the overproduction of abnormal immunoglobulins, which overcrowd the bone marrow and cause decreased production of other cell lines such as red blood cells. Symptoms of anemia include fatigue, weakness, shortness of breath, pallor, and tachycardia. A complete blood count with differential typically reveals normocytic (i.e., the size of the red blood cells is normal) anemia with hemoglobin < 12 g/dl. If anemia is a side effect of chemotherapy, the dose may be adjusted or another regimen may be chosen. Erythropoietin is a treatment option that helps the body produce more red blood cells. If the anemia is severe enough, a blood transfusion may be warranted.

What does the “B” in CRAB mean?

The “B” in CRAB refers to bone pain secondary to plasma cell infiltration in the bones. This is commonly experienced in areas such as the back, ribs, and hips. The myeloma cells weaken and destroy bone tissue, leading to bone pain, osteoporosis, and fractures. Treatment consists of bisphosphonates (e.g., zoledronic acid) which inhibit osteoclasts’ role in bone resorption and prevent complications such as bone fractures.

What are the most important facts to know about the CRAB acronym?

Multiple myeloma is a cancer of the plasma cell (i.e., a specific type of white blood cell of the immune system that produces antibodies to fight infections) of the bone marrow. Multiple myeloma belongs to a family of plasma cell disorders, which are either acquired or inherited disorders resulting in excess production of a single type of immunoglobulin. People who develop multiple myeloma can either inherit a genetic mutation that predisposes them to the condition or develop it later in life from exposure to risk factors (e.g., prior radiation therapy exposure or excess alcohol use). CRAB is an acronym that highlights the clinical signs and symptoms associated with multiple myeloma. These include calcium elevation, renal dysfunction, anemia, and bone pain.

References

Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma: Spotlight review. Leukemia. 2009;23(12):2210-2221. doi:10.1038/leu.2009.174

International Myeloma Foundation. Accessed April 12, 2024.
https://www.myeloma.org/

Merck Manuals: Overview of plasma cell disorders. Accessed April 12, 2024.
https://www.merckmanuals.com/home/blood-disorders/plasma-cell-disorders/overview-of-plasma-cell-disorders

Osmosis: Multiple myeloma: Clinical sciences. (2024, 6/24). Retrieved from (https://www.osmosis.org/learn/Multiple_myeloma:_Clinical_sciences).

Rajkumar SV, Gertz MA, Kyle RA. Primary systemic amyloidosis with delayed progression to multiple myeloma. Cancer. 1998;82(8):1501-1505.