Given that the history, patient symptoms, and physical signs are nonspecific and infrequently seen in patients with amyloid, when should a clinician consider this diagnosis and begin screening procedures?

The 4 most common clinical settings in which amyloid should be part of the differential diagnosis are:

Whenever an adult presents you with 1 of these 4 syndromes, amyloidosis must be considered.

The source of the amyloid protein is a population of monoclonal plasma cells in the bone marrow. Therefore, when a patient is seen with nephrotic-range proteinuria, unexplained heart failure, hepatomegaly, or peripheral neuropathy, the most important screening test would be immunoelectrophoresis and immunofixation of the serum and urine along with Free Kappa and Lambda Light Chain Assay (Freelite™). Immunofixation should be done on both serum and urine because a monoclonal protein is absent from the serum in one-third of patients and is absent from the urine in one-third of patients. A simple screening electrophoresis is also inadequate because a high proportion of patients with amyloidosis have free light chains in the serum or urine rather than an intact immunoglobulin molecule. The presence of free light chains in the serum or in the urine generally does not produce a visible peak on the electrophoretic pattern and may be overlooked. Moreover, even when a small peak is present in urine, heavy proteinuria frequently seen in amyloidosis patients obscures its presence. When both serum and urine are subjected to immunofixation, a monoclonal protein will be found in nearly 90% of patients. This makes it an excellent screening test, which has the advantage of being inexpensive and noninvasive. In addition, the Freelite™ should be performed. When a monoclonal protein is found in the serum or urine of a patient under investigation for proteinuria, cardiac dysfunction, hepatomegaly, or neuropathy, the likelihood of amyloidosis is high.

Confirmation of the Diagnosis of Amyloidosis

Once a patient with a compatible clinical syndrome is found to have a monoclonal protein, biopsy proof is necessary to establish the diagnosis unequivocally. Because amyloidosis is a systemic disorder with a high prevalence of widespread vascular deposits, biopsy of a visceral organ is generally not required. Biopsy of the kidney, endomyocardium, liver, or sural nerve certainly establishes a diagnosis of amyloidosis, but it is not preferred and is not required. Biopsy sites that have been reported to have a high prevalence of positive staining with Congo red in patients with the disease include the minor salivary glands, the gingiva, the rectum, the bone marrow, and the subcutaneous fat. In Japan, random endoscopic biopsies of stomach demonstrate amyloid deposits in 90% of patients.