What are the CRAB (Hypercalcemia, Renal failure, Anemia, Bone lesions) criteria for multiple myeloma?

CRAB Criteria for Multiple Myeloma

The CRAB criteria for multiple myeloma consist of hypercalcemia, renal insufficiency, anemia, and bone lesions, which define end-organ damage attributable to the plasma cell proliferative disorder and are essential for diagnosing symptomatic multiple myeloma requiring treatment. 1

Detailed CRAB Criteria

The specific thresholds for each CRAB criterion are:

Hypercalcemia (C)

• Serum calcium >11.5 mg/dl (>2.875 mmol/L) 1

Renal Insufficiency (R)

• Serum creatinine >1.73 μmol/l (>2 mg/dl) or
• Estimated creatinine clearance <40 ml/min 1

Anemia (A)

• Normochromic, normocytic anemia with either:
  • Hemoglobin value ≥2 g/dl below the lower limit of normal, or
  • Hemoglobin value <10 g/dl 1

Bone Lesions (B)

• Lytic lesions
• Severe osteopenia
• Pathologic fractures 1

Clinical Significance of CRAB Criteria

The CRAB criteria are crucial for:

1. Distinguishing between plasma cell disorders: They help differentiate symptomatic multiple myeloma from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma 1, 2

2. Treatment decisions: Treatment should be initiated in all patients with active myeloma fulfilling the CRAB criteria, as these indicate end-organ damage requiring intervention 1

3. Prognostic implications: Among CRAB features, bone disease is the most common factor and may have the strongest prognostic value in symptomatic myeloma patients treated with novel agents 3

Diagnostic Framework

For a diagnosis of multiple myeloma, all of these criteria must be met:

• Clonal bone marrow plasma cells ≥10% or biopsy-proven plasmacytoma, AND
• Evidence of end-organ damage (CRAB) that can be attributed to the underlying plasma cell proliferative disorder 1, 4

Important Clinical Considerations

• Updated criteria: In 2014, the International Myeloma Working Group updated the diagnostic criteria to include three additional biomarkers that can define multiple myeloma even in the absence of CRAB features:

  • Clonal bone marrow plasma cell percentage ≥60%
  • Involved:uninvolved serum free light chain ratio ≥100 (provided involved FLC is ≥100 mg/L)

  • 1 focal lesion on MRI studies (≥5 mm in size) 5, 4, 6

• Differential diagnosis: While CRAB features are characteristic of multiple myeloma, they are not pathognomonic. In rare cases, lymphoma and other malignancies can present with similar features 7

• Evaluation of suspected cases: A comprehensive diagnostic workup should include serum protein electrophoresis, immunofixation, bone marrow assessment, and appropriate imaging studies to evaluate for bone lesions 2

• Treatment implications: The presence of CRAB criteria indicates the need for immediate treatment, whereas their absence in patients with monoclonal gammopathy suggests observation rather than intervention 1

Clinical Pitfalls to Avoid

1. Attributing CRAB features to other causes: Ensure that end-organ damage is attributed to the plasma cell disorder and not to other medical conditions

2. Missing subtle bone lesions: Conventional radiography may miss early bone lesions; consider advanced imaging (MRI or CT) when clinical suspicion is high despite negative skeletal survey

3. Overlooking renal dysfunction: Even mild elevations in creatinine can be significant in the context of a plasma cell disorder

4. Neglecting to monitor for CRAB development: Patients with MGUS or smoldering myeloma require regular monitoring for the development of CRAB features, as this would indicate progression to symptomatic disease requiring treatment