What are the CRAB (Hypercalcemia, Renal impairment, Anemia, Bone lesions) criteria?

CRAB Criteria Definition

CRAB criteria are the four cardinal manifestations of end-organ damage in multiple myeloma: hypercalcemia (C), renal insufficiency (R), anemia (A), and bone lesions (B)—the presence of any one criterion attributable to plasma cell disorder confirms symptomatic myeloma requiring treatment. 1

Specific Diagnostic Thresholds

Hypercalcemia (C)

• Serum calcium >11.5 mg/dL 2, 1, 3

Renal Insufficiency (R)

• Serum creatinine >2 mg/dL (>1.73 μmol/L) OR
• Creatinine clearance <40 mL/min 2, 1, 3

Anemia (A)

• Hemoglobin <10 g/dL OR
• Hemoglobin ≥2 g/dL below the lower limit of normal 2, 1, 3
• Must be normochromic and normocytic 2

Bone Lesions (B)

• Lytic lesions on skeletal imaging OR
• Severe osteopenia OR
• Pathologic fractures 2, 1, 3

Clinical Application

Diagnostic Context

CRAB criteria distinguish symptomatic multiple myeloma from asymptomatic conditions when combined with ≥10% clonal bone marrow plasma cells or biopsy-proven plasmacytoma. 2, 1 The International Myeloma Society requires that end-organ damage must be attributable to the underlying plasma cell disorder, not other causes. 1

Treatment Trigger

Treatment must be initiated immediately in all patients fulfilling CRAB criteria, as these represent active myeloma with end-organ damage. 2, 4 Delaying treatment in patients with clear CRAB criteria increases morbidity and mortality. 4

Differential Diagnosis Framework

• MGUS (Monoclonal Gammopathy of Undetermined Significance): Serum monoclonal protein <3 g/dL, clonal bone marrow plasma cells <10%, and absence of CRAB criteria—no treatment required 2, 3
• Smoldering Multiple Myeloma: Serum monoclonal protein ≥3 g/dL and/or clonal bone marrow plasma cells ≥10%, but absence of CRAB criteria—closer monitoring required but no immediate treatment 2, 3
• Symptomatic Multiple Myeloma: ≥10% clonal plasma cells AND presence of any CRAB criterion—treatment mandatory 2, 1

Critical Pitfalls

Non-Specificity Warning

CRAB criteria are not pathognomonic of multiple myeloma—lymphoma and other malignancies can present with identical features. 5 Always confirm with serum/urine protein electrophoresis, immunofixation, bone marrow examination with CD138 staining, and cytogenetic studies before initiating myeloma-specific therapy. 1, 3

Prognostic Implications

Among CRAB features in the novel agent era, hypercalcemia and bone disease confer significantly worse prognosis, while anemia and renal failure show no difference in survival when treated with modern regimens. 6 Bone disease is the most common CRAB feature and may have the strongest prognostic value. 6

Imaging Considerations

Skeletal survey should no longer be used as the sole imaging modality—whole-body low-dose CT is more cost-effective for initial assessment, while whole-body MRI is most sensitive for detecting bone involvement. 7