Beyond the CRAB symptoms: a study of presenting clinical manifestations of multiple myeloma

Although the typical clinical manifestations of multiple myeloma (MM) are summarized by the CRAB symptoms (hypercalcemia, renal insufficiency, anemia, and bone lesions), a significant proportion of patients with MM present with a variety of other clinical manifestations. We conducted a study evaluating the presenting symptoms that led to the diagnosis of MM.

We conducted a retrospective review of 170 consecutive patients with MM seen at the Penn State Hershey Cancer Institute.

Among patients with symptomatic MM, 74% presented with CRAB symptoms, 20% presented with non-CRAB manifestations, and 6% had both clinical features. Ten categories of non-CRAB manifestations were found, in order of decreasing frequency: neuropathy (because of spinal cord compression, nerve root compression, or peripheral neuropathy), extramedullary involvement, hyperviscosity syndrome, concomitant amyloidosis (eg, nephrotic syndrome or cardiopathy), hemorrhage/coagulopathy, systemic symptoms (eg, fever or weight loss), primary plasma cell leukemia, infections, cryoglobulinemia, and secondary gout. Kaplan-Meier estimates of survival in patients with non-CRAB manifestations did not show a significant difference from the survival of patients presenting with CRAB symptoms.

Presenting symptoms of MM may be grouped in a total of 14 categories, 4 for the CRAB and 10 for the less common non-CRAB features. Grouped together, non-CRAB manifestations do not appear to confer a negative effect on the prognosis of patients with MM.